Reflecting the causes of variability of EEG responses elicited by cerebellar TMS.

Recently, Fong et al. published EEG responses in cerebral cortex elicited by cerebellar TMS (cbTMS) (Fong et al., 2023), which differ from our recently identified cbTMS-EEG responses (Gassmann et al., 2022). Fong et al. argued that this discrepancy is due to coil placement unsuitable for eliciting cerebellar brain inhibition (CBI) in our study. However, we reliably elicited CBI in our subjects. Consequently, this leads to a compelling discussion on possible reasons for the observed discrepancies in cbTMS-evoked EEG responses. Reliably measuring cbTMS-evoked EEG responses could become an important neurophysiological tool to test effective cerebellum-to-cortex connectivity.

Assessing effective connectivity of the cerebellum with cerebral cortex using TMS-EEG.

BACKGROUND AND OBJECTIVES: The cerebellum provides important input to the cerebral cortex but its assessment is difficult. Cerebellar brain inhibition tested by paired-coil transcranial magnetic stimulation (TMS) is limited to the motor cortex. Here we sought to measure responses to cerebellar TMS (cbTMS) throughout the cerebral cortex using electroencephalography (EEG). METHODS: Single-pulse TMS was applied with an induced upward current to the right cerebellar hemisphere in 46 healthy volunteers while recording EEG. Multiple control conditions, including TMS of right occipital cortex, cbTMS with induced downward current, and a sham condition modified specifically for cbTMS were tested to provide evidence for the specificity of the EEG responses evoked by cbTMS with an upward induced current. RESULTS: Distinct EEG response components could be specifically attributed to cbTMS, namely a left-hemispheric prefrontal positive deflection 25 ms after cbTMS, and a subsequent left-hemispheric parietal negative deflection peaking at 45 ms. In the time-frequency-response analysis, cbTMS induced a left-hemispheric prefrontal power increase in the high-beta frequency band. These responses were not seen in the control and sham conditions. CONCLUSIONS: The EEG responses observed in this highly controlled experimental design may cautiously be attributed to reflect specific signatures of the activation of the cerebello-dentato-thalamo-cortical pathway by cbTMS. Therefore, these responses may provide biomarkers for assessing the integrity of this pathway, a proposition that will need further testing in clinical populations.

µ-rhythm phase from somatosensory but not motor cortex correlates with corticospinal excitability in EEG-triggered TMS.

BACKGROUND: 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. OBJECTIVE/HYPOTHESIS: 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. NEW METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

Prefrontal theta phase-dependent rTMS-induced plasticity of cortical and behavioral responses in human cortex.

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.

Prefrontal Theta-Phase Synchronized Brain Stimulation With Real-Time EEG-Triggered TMS.

BACKGROUND: Theta-band neuronal oscillations in the prefrontal cortex are associated with several cognitive functions. Oscillatory phase is an important correlate of excitability and phase synchrony mediates information transfer between neuronal populations oscillating at that frequency. The ability to extract and exploit the prefrontal theta rhythm in real time in humans would facilitate insight into neurophysiological mechanisms of cognitive processes involving the prefrontal cortex, and development of brain-state-dependent stimulation for therapeutic applications. OBJECTIVES: We investigate individual source-space beamforming-based estimation of the prefrontal theta oscillation as a method to target specific phases of the ongoing theta oscillations in the human dorsomedial prefrontal cortex (DMPFC) with real-time EEG-triggered transcranial magnetic stimulation (TMS). Different spatial filters for extracting the prefrontal theta oscillation from EEG signals are compared and additional signal quality criteria are assessed to take into account the dynamics of this cortical oscillation. METHODS: Twenty two healthy participants were recruited for anatomical MRI scans and EEG recordings with 18 composing the final analysis. We calculated individual spatial filters based on EEG beamforming in source space. The extracted EEG signal was then used to simulate real-time phase-detection and quantify the accuracy as compared to post-hoc phase estimates. Different spatial filters and triggering parameters were compared. Finally, we validated the feasibility of this approach by actual real-time triggering of TMS pulses at different phases of the prefrontal theta oscillation. RESULTS: Higher phase-detection accuracy was achieved using individualized source-based spatial filters, as compared to an average or standard Laplacian filter, and also by detecting and avoiding periods of low theta amplitude and periods containing a phase reset. Using optimized parameters, prefrontal theta-phase synchronized TMS of DMPFC was achieved with an accuracy of ±55°. CONCLUSION: This study demonstrates the feasibility of triggering TMS pulses during different phases of the ongoing prefrontal theta oscillation in real time. This method is relevant for brain state-dependent stimulation in human studies of cognition. It will also enable new personalized therapeutic repetitive TMS protocols for more effective treatment of neuropsychiatric disorders.

TMS-EEG signatures of glutamatergic neurotransmission in human cortex.

Neuronal activity in the brain reflects an excitation-inhibition balance that is regulated predominantly by glutamatergic and GABAergic neurotransmission, and often disturbed in neuropsychiatric disorders. Here, we tested the effects of a single oral dose of two anti-glutamatergic drugs (dextromethorphan, an NMDA receptor antagonist; perampanel, an AMPA receptor antagonist) and an L-type voltage-gated calcium channel blocker (nimodipine) on transcranial magnetic stimulation (TMS)-evoked electroencephalographic (EEG) potentials (TEPs) and TMS-induced oscillations (TIOs) in 16 healthy adults in a pseudorandomized, double-blinded, placebo-controlled crossover design. Single-pulse TMS was delivered to the hand area of left primary motor cortex. Dextromethorphan increased the amplitude of the N45 TEP, while it had no effect on TIOs. Perampanel reduced the amplitude of the P60 TEP in the non-stimulated hemisphere, and increased TIOs in the beta-frequency band in the stimulated sensorimotor cortex, and in the alpha-frequency band in midline parietal channels. Nimodipine and placebo had no effect on TEPs and TIOs. The TEP results extend previous pharmaco-TMS-EEG studies by demonstrating that the N45 is regulated by a balance of GABAAergic inhibition and NMDA receptor-mediated glutamatergic excitation. In contrast, AMPA receptor-mediated glutamatergic neurotransmission contributes to propagated activity reflected in the P60 potential and midline parietal induced oscillations. This pharmacological characterization of TMS-EEG responses will be informative for interpreting TMS-EEG abnormalities in neuropsychiatric disorders with pathological excitation-inhibition balance.

Efficacy and Safety of Transcranial Direct Current Stimulation for Treating Negative Symptoms in Schizophrenia: A Randomized Clinical Trial.

Importance: Negative symptoms represent a substantial burden in schizophrenia. Although preliminary studies have suggested that transcranial direct current stimulation (tDCS) is effective for some clusters of symptoms, the clinical benefits for negative symptoms are unclear. Objective: To determine the efficacy and safety of tDCS vs sham as an add-on treatment for patients with schizophrenia and predominant negative symptoms. Design, Setting, and Participants: The double-blind Schizophrenia Treatment With Electric Transcranial Stimulation (STARTS) randomized clinical trial was conducted from September 2014 to March 2018 in 2 outpatient clinics in the state of São Paulo, Brazil. Patients with schizophrenia with stable negative and positive symptoms and a minimum score of 20 points in the negative symptoms subscale of the Positive and Negative Syndrome Scale (PANSS) were included. Interventions: Ten sessions of tDCS performed twice a day for 5 days or a sham procedure. The anode and the cathode were positioned over the left prefrontal cortex and the left temporoparietal junction, respectively. Main Outcomes and Measures: Change in the PANSS negative symptoms subscale score at week 6 was the primary outcome. Patients were followed-up for an additional 6 weeks. Results: Of the 100 included patients, 20 (20.0%) were female, and the mean (SD) age was 35.3 (9.3) years. A total of 95 patients (95.0%) finished the trial. In the intention-to-treat analysis, patients receiving active tDCS showed a significantly greater improvement in PANSS score compared with those receiving the sham procedure (difference, 2.65; 95% CI, 1.51-3.79; number needed to treat, 3.18; 95% CI, 2.12-6.99; P < .001). Response rates for negative symptoms (20% improvement or greater) were also higher in the active group (20 of 50 [40%]) vs the sham group (2 of 50 [4%]) (P < .001). These effects persisted at follow-up. Transcranial direct current stimulation was well tolerated, and adverse effects did not differ between groups, except for burning sensation over the scalp in the active group (43.8%) vs the sham group (14.3%) (P = .003). Conclusions and Relevance: Transcranial direct current stimulation was effective and safe in ameliorating negative symptoms in patients with schizophrenia. Trial Registration: ClinicalTrials.gov identifier: NCT02535676.

Brain oscillation-synchronized stimulation of the left dorsolateral prefrontal cortex in depression using real-time EEG-triggered TMS.

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.

Brain State-dependent Brain Stimulation with Real-time Electroencephalography-Triggered Transcranial Magnetic Stimulation.

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.

Schizophrenia TreAtment with electRic Transcranial Stimulation (STARTS): design, rationale and objectives of a randomized, double-blinded, sham-controlled trial.

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 .

Schizophrenia TreAtment with electRic Transcranial Stimulation (STARTS): design, rationale and objectives of a randomized, double-blinded, sham-controlled trial / Tratamento da esquizofrenia com estimulação transcraniana por corrente contínua (ETCC): fundamentação teórica e objetivos de um ensaio clínico randomizado, duplo-cego, controlado por simulação

Abstract 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.

Changes in motor cortical excitability in schizophrenia following transcranial direct current stimulation.

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 (ß = -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.

Nil effects of µ-rhythm phase-dependent burst-rTMS on cortical excitability in humans: A resting-state EEG and TMS-EEG study.

Repetitive transcranial magnetic stimulation (rTMS) can induce excitability changes of a stimulated brain area through synaptic plasticity mechanisms. High-frequency (100 Hz) triplets of rTMS synchronized to the negative but not the positive peak of the ongoing sensorimotor µ-rhythm isolated with the concurrently acquired electroencephalography (EEG) resulted in a reproducible long-term potentiation like increase of motor evoked potential (MEP) amplitude, an index of corticospinal excitability (Zrenner et al. 2018, Brain Stimul 11:374-389). Here, we analyzed the EEG and TMS-EEG data from (Zrenner et al., 2018) to investigate the effects of µ-rhythm-phase-dependent burst-rTMS on EEG-based measures of cortical excitability. We used resting-state EEG to assess µ- and ß-power in the motor cortex ipsi- and contralateral to the stimulation, and single-pulse TMS-evoked and induced EEG responses in the stimulated motor cortex. We found that µ-rhythm-phase-dependent burst-rTMS did not significantly change any of these EEG measures, despite the presence of a significant differential and reproducible effect on MEP amplitude. We conclude that EEG measures of cortical excitability do not reflect corticospinal excitability as measured by MEP amplitude. Most likely this is explained by the fact that rTMS induces complex changes at the molecular and synaptic level towards both excitation and inhibition that cannot be differentiated at the macroscopic level by EEG.

Comparison of cortical EEG responses to realistic sham versus real TMS of human motor cortex.

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.

Modulation of cortical responses by transcranial direct current stimulation of dorsolateral prefrontal cortex: A resting-state EEG and TMS-EEG study.

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.

Validation of the National Institute of Neurological Disorders and Stroke Criteria for Psychosis in Parkinson Disease.

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.

The impact of temperament and character inventory personality traits on long-term outcome of Roux-en-Y gastric bypass.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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/m(2) (±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. CONCLUSIONS: 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.

Avaliação longitudinal psicopatológica e de personalidade de pacientes submetidos à cirurgia bariátrica: implicações prognósticas / Longitudinal evaluation of patients undergone bariatric surgery using psychopathological and personality veriables: prognostic implications

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"...

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...

Weight gain, metabolic disturbances, and physical health care in a Brazilian sample of outpatients with schizophrenia.

BACKGROUND: In the last few decades, a large number of studies have produced compelling evidence that patients with schizophrenia are at increased risk for developing several medical conditions and diseases, including obesity, metabolic disturbances, and cardiovascular diseases. Several protocols have been designed with the aim of reducing such risk. OBJECTIVE: To investigate current physical health status in a population of outpatients with schizophrenia. METHODS: A cross-sectional study was conducted in our outpatient clinic, selecting subjects who met DSM-IV diagnosis criteria for schizophrenia. Data were collected regarding clinical characteristics, lifestyle, medication in use, and biometric and laboratory parameters. RESULTS: A total of 261 patients were included. We found a high prevalence of elevated body mass index (BMI . 25) (70%), dyslipidemia (73.2%), and metabolic syndrome (28.7%). Patients' ages were associated with worsened lipid profiles, but other variables, such as disorder duration or type of antipsychotic in use, were not associated with any metabolic disturbance. Despite the increased prevalence of these conditions, only a small portion of the sample was under regular medical treatment. CONCLUSION: Outpatients with schizophrenia show signs of poor physical health conditions. These findings reinforce the need for an intensive and appropriate approach to assure that these patients receive adequate clinical referral and treatment.