A real-world retrospective cohort study comparing two bilateral stimulation protocols of add-on rTMS in patients with treatment resistant depression and severe anxiety.

BACKGROUND: Transcranial magnetic stimulation (TMS) has been shown to improve response and remission in patients with treatment resistant depression. The objective of this study was to compare the efficacy of two bilateral rTMS protocols with different protocols in patients with treatment resistant depression and comorbid severe anxiety. METHODS: A retrospective cohort study involving 67 patients who underwent two different bilateral TMS protocols and who met the specified eligibility criteria was conducted. Group 1 received stimulation with 85% RMT intermittent theta burst (iTBS) in the left DLPFC + 120% RMT (1 Hz) in the right DLPFC. Group 2 received stimulation with 100% RMT (iTBS) in the left DLPFC + 110% RMT (1 Hz) in the left DLPFC. RESULTS: After the magnetic stimulation treatment, 55% (n=22) achieved response to depression symptoms in group 1 and 62% (n=18) in group 2. Remission of depression symptoms was achieved in 13% in group 1 (n=5) and 24% in group 2 (n=7). There were no significant differences between the two protocols after TMS CONCLUSIONS: Different bilateral protocol parameters in individuals undergoing TMS may have an impact on symptom response and remission. Further studies with larger sample sizes are needed.

Estimulação Transcraniana para Transtornos do Sono: uma revisão sistemática / Transcranial Stimulation in Sleep Disorders: a systematic review / Estimulación Transcraneal para los Trastornos del Sueño: una revisión sistemática

Os transtornos do sono podem ter várias consequências para a cognição, comportamento e vida social das pessoas. No entanto, a terapia utilizada para avaliar e intervir nesses transtornos ainda não está consolidada. Nesse contexto, o objetivo deste estudo foi verificar a aplicabilidade e eficácia da estimulação transcraniana (ETCA / ETCC / EMTr) nos transtornos do sono. Foi realizada uma busca sistemática de acordo com as diretrizes do PRISMA nas bases de dados Web of Science, PubMed, LILACS e SciELO. Inicialmente, foram encontrados 448 artigos, de acordo com os critérios de elegibilidade. O banco de dados de evidências de fisioterapia (PEDro) foi utilizado para avaliar a qualidade metodológica dos 11 artigos finais. Em geral, os resultados indicam que há tanto relatos favoráveis quanto desfavoráveis à eficácia do uso terapêutico das técnicas de estimulação transcraniana nos transtornos do sono e, portanto, ainda se configura como uma questão em aberto, dependendo de múltiplos fatores metodológicos e conceituais.

Sleep disorders can have several consequences on people's cognition, behavior and social life. However, the therapy used to assess and intervene in these disorders is not yet consolidated. In this context, the aim of this study was to verify the applicability and effectiveness of transcranial stimulation (tACS / tDCS / rTMS) in sleep disorders. A systematic search was performed according to PRISMA guidelines in the Web of Science, PubMed, LILACS, and SciELO databases. Initially, 448 articles were found, according to the eligibility criteria. The physiotherapy evidence database (PEDro) was used to assess the methodological quality of the 11 final articles. In general, the results indicate that there are both favorable and unfavorable reports on the effectiveness of the therapeutic use of transcranial stimulation techniques in sleep disorders and, therefore, it is still an open question, depending on multiple methodological and conceptual factors.

Trastornos del sueño pueden tener varias consecuencias para la cognición, el comportamiento y la vida social de las personas. La terapia utilizada para evaluar e intervenir en estos trastornos aún no está consolidada. En este contexto, el objetivo de este estudio fue verificar la aplicabilidad y efectividad de la estimulación transcraneal (ETCA / ETCC / EMTr) en los trastornos del sueño. Se realizó una búsqueda sistemática según las guías PRISMA en las bases de datos Web of Science, PubMed, LILACS y SciELO. Inicialmente se encontraron 448 artículos, según los criterios de elegibilidad. Se utilizó la base de datos PEDro para evaluar la calidad metodológica de los 11 artículos finales. En general, los resultados indican que existen informes tanto favorables como desfavorables sobre la efectividad del uso terapéutico de las técnicas de estimulación transcraneal en los trastornos del sueño y, por tanto, sigue siendo una cuestión abierta, dependiendo de múltiples factores metodológicos y conceptuales.

Treatment of depression in the elderly with repetitive transcranial magnetic stimulation using theta-burst stimulation: Study protocol for a randomized, double-blind, controlled trial.

Introduction: Transcranial magnetic stimulation (TMS) is a consolidated procedure for the treatment of depression, with several meta-analyses demonstrating its efficacy. Theta-burst stimulation (TBS) is a modification of TMS with similar efficacy and shorter session duration. The geriatric population has many comorbidities and a high prevalence of depression, but few clinical trials are conducted specifically for this age group. TBS could be an option in this population, offering the advantages of few side effects and no pharmacological interactions. Therefore, our aim is to investigate the efficacy of TBS in geriatric depression. Clinical trial registration: [https://clinicaltrials.gov/ct2/], identifier [NCT04842929].

Somatosensory Cortex Repetitive Transcranial Magnetic Stimulation and Associative Sensory Stimulation of Peripheral Nerves Could Assist Motor and Sensory Recovery After Stroke.

Background: We investigated whether transcranial magnetic stimulation (rTMS) over the primary somatosensory cortex (S1) and sensory stimulation (SS) could promote upper limb recovery in participants with subacute stroke. Methods: Participants were randomized into four groups: rTMS/Sham SS, Sham rTMS/SS, rTMS/SS, and control group (Sham rTMS/Sham SS). Participants underwent ten sessions of sham or active rTMS over S1 (10 Hz, 1,500 pulses, 120% of resting motor threshold, 20 min), followed by sham or active SS. The SS involved active sensory training (exploring features of objects and graphesthesia, proprioception exercises), mirror therapy, and Transcutaneous electrical nerve stimulation (TENS) in the region of the median nerve in the wrist (stimulation intensity as the minimum intensity at which the participants reported paresthesia; five electrical pulses of 1 ms duration each at 10 Hz were delivered every second over 45 min). Sham stimulations occurred as follows: Sham rTMS, coil was held while disconnected from the stimulator, and rTMS noise was presented with computer loudspeakers with recorded sound from a real stimulation. The Sham SS received therapy in the unaffected upper limb, did not use the mirror and received TENS stimulation for only 60 seconds. The primary outcome was the Body Structure/Function: Fugl-Meyer Assessment (FMA) and Nottingham Sensory Assessment (NSA); the secondary outcome was the Activity/Participation domains, assessed with Box and Block Test, Motor Activity Log scale, Jebsen-Taylor Test, and Functional Independence Measure. Results: Forty participants with stroke ischemic (n = 38) and hemorrhagic (n = 2), men (n = 19) and women (n = 21), in the subacute stage (10.6 ± 6 weeks) had a mean age of 62.2 ± 9.6 years, were equally divided into four groups (10 participants in each group). Significant somatosensory improvements were found in participants receiving active rTMS and active SS, compared with those in the control group (sham rTMS with sham SS). Motor function improved only in participants who received active rTMS, with greater effects when active rTMS was combined with active SS. Conclusion: The combined use of SS with rTMS over S1 represents a more effective therapy for increasing sensory and motor recovery, as well as functional independence, in participants with subacute stroke. Clinical Trial Registration: [clinicaltrials.gov], identifier [NCT03329807].

Differential involvement of left and right frontoparietal areas in visuospatial planning: An rTMS study.

The planning process consists of pre-determining an ordered series of actions to accomplish a goal. Previous research showed that the left prefrontal cortex (PFC) is likely to create the strategy for a plan, while the right PFC could be relevant for its update. These roles for the two PFCs need to be ascertained for visuospatial planning, whether communalities or differences exist with other planning tasks. Moreover, the contribution of the posterior parietal cortex (PPC) to planning still lacks evidence. Online repetitive transcranial magnetic stimulation (1 Hz) was used, and 32 participants were involved in the visuospatial planning task in a within-subject design to inhibit either the frontal or the parietal cortex of either the left or the right hemisphere. The goal consisted of evaluating the contribution of these cortical regions, also controlling for gender, in a computerized version of the travelling salesman problem (TSP), the "Maps" task. The results showed that all the stimulated sites produced significant differences in their involvement, reflected in several parameters (such as initial planning and execution times, strategies and heuristics used), with respect to the control group. The roles for the two PFCs were generally confirmed in all measures except path length, while the contribution of the PPC emerged throughout the measures related to the ongoing execution. We concluded that the results obtained with the TSP paradigm were consistent with results obtained using other tasks used to study the planning process (such as the Tower of London) for the evaluation of PFC contribution. In addition, we showed that the contribution of the PPC to the planning process has probably been underestimated.

Estimulación Magnética Trascraneal "Theta-Burst Intermitente" en un paciente con Trastorno del Espectro Autista: Reporte de un caso / Intermittent Theta-Burst Transcranial Magnetic Stimulation in a Patient with Autism Spectrum Disorder: A Case Report

Resumen Introducción: La estimulación magnética transcraneal (EMT) es una opción potencial de tratamiento para la sintomatología de trastorno del espectro autista. Objetivos: Determinar la eficacia de la EMT en modalidad theta-burst intermitente (ETBi) sobre la corteza pre frontal dorso lateral izquierda (CDLPF) en el manejo de comportamientos patológicos asociados con TEA. Pacientes y Métodos: Paciente masculino de 10 años de edad diagnosticado con TEA con (ADOS) Autistic Diagnostic Observation Schedule, presenta una historia familiar de una hermana menor con TEA. Tanto el estudio de Resonancia Magnética encéfalo (IRM) y IRM funcional (IRMf) con paradigma emocionales se efectuaron antes del tratamiento de ETBi, inmediatamente después de tratamiento ETBi, y después de 6 meses de tratamiento con ETBi. Resultados: La prueba de ATEC reporto mejoría en las escalas de comunicación, cognición, social y comportamiento, 83%,81%,72% y 52% respectivamente. La puntuación total mejoro un 66% inmediatamente después de tratamiento y 55% en un periodo de 6 meses. La IRMf revelo la activación de la corteza frontal, parietal y occipital antes del tratamiento con ETBi y persistiendo la mejoría por 6 meses. Conclusión: ETBi una técnica de neuromodulación no invasiva bien tolerado que requiere un tiempo de administración menor que el tratamiento estándar.

Abstract Background: Transcranial magnetic stimulation (TMS) is a potential treatment option for autism spectrum disorder (ASD) symptomatology. Objectives: To determine the efficacy of the TMS intermittent theta-burst stimulation (iTBS) protocol over the left dorsolateral prefrontal cortex (DLPFC) in the management of pathological behaviors associated with ASD. Patient/Methods: A 10-year-old male diagnosed with ASD by the Autism Diagnostic Observation Schedule (ADOS) presented with a family history of ASD with a younger sister diagnosed with the same disorder. Both magnetic resonance imaging (MRI) and functional MRI (fMRI) scans for emotional paradigms were performed before the iTBS treatment, immediately after the iTBS treatment, and after 6 months of iTBS treatment. Results: The ATEC reports revealed improvement in communication, cognition, sociability, and behavior scales by 83%, 81%, 72%, and 52%, respectively. The overall score improved by 66% immediately after the treatment and by 55% lasting over a 6-month period. The fMRI revealed the activation of the frontal, parietal, and occipital cortex before iTBS treatment, and a better integration and activation of the frontal, temporal, and occipital cortex after iTBS treatment and persisted after 6 months. Conclusions: iTBS is a well-tolerated, non-invasive neuromodulation technique that requires relatively less administration than the standard treatment.

Latin American and Caribbean consensus on noninvasive central nervous system neuromodulation for chronic pain management (LAC2-NIN-CP).

INTRODUCTION: Chronic pain (CP) is highly prevalent and generally undertreated health condition. Noninvasive brain stimulation may contribute to decrease pain intensity and influence other aspects related to CP. OBJECTIVE: To provide consensus-based recommendations for the use of noninvasive brain stimulation in clinical practice. METHODS: Systematic review of the literature searching for randomized clinical trials followed by consensus panel. Recommendations also involved a cost-estimation study. RESULTS: The systematic review wielded 24 transcranial direct current stimulation (tDCS) and 22 repetitive transcranial magnetic stimulation (rTMS) studies. The following recommendations were provided: (1) Level A for anodal tDCS over the primary motor cortex (M1) in fibromyalgia, and level B for peripheral neuropathic pain, abdominal pain, and migraine; bifrontal (F3/F4) tDCS and M1 high-definition (HD)-tDCS for fibromyalgia; Oz/Cz tDCS for migraine and for secondary benefits such as improvement in quality of life, decrease in anxiety, and increase in pressure pain threshold; (2) level A recommendation for high-frequency (HF) rTMS over M1 for fibromyalgia and neuropathic pain, and level B for myofascial or musculoskeletal pain, complex regional pain syndrome, and migraine; (3) level A recommendation against the use of anodal M1 tDCS for low back pain; and (4) level B recommendation against the use of HF rTMS over the left dorsolateral prefrontal cortex in the control of pain. CONCLUSION: Transcranial DCS and rTMS are recommended techniques to be used in the control of CP conditions, with low to moderate analgesic effects, and no severe adverse events. These recommendations are based on a systematic review of the literature and a consensus made by experts in the field. Readers should use it as part of the resources available to decision-making.

Low-frequency rTMS stimulation over superior parietal cortex medially improves time reproduction and increases the right dorsolateral prefrontal cortex predominance.

AIM OF THE STUDY: Previous studies have shown that several cortical regions are involved in temporal tasks in multiple timescales. However, the hemispheric predominance of the dorsolateral prefrontal cortex (DLPFC) during time reproduction after repetitive low-frequency transcranial magnetic stimulation (rTMS) is relatively unexplored. Here, we study the effects of 1 Hz rTMS and sham stimulation applied medially over the superior parietal cortex (SPC) on the DLPFC alpha and beta band asymmetry and on time reproduction. MATERIALS AND METHODS: For this purpose, we have combined rTMS with electroencephalography in 20 healthy subjects who performed the time reproduction task in two conditions (sham and 1 Hz). RESULTS: The worst performance was observed in sham and 1Hz conditions for longer time intervals (p < .05), with the 1Hz condition subjects sub-reproducing the time interval, closer to the target interval (p < .05). The right DLPFC hemispheric predominance was found in both conditions, but after low-frequency rTMS, the right hemisphere predominance increased in the 1Hz condition (p < .05). CONCLUSIONS: Results of this study suggest that rTMS applied over the SPC influences time interval interpretation and the DLPFC functions. Future studies would explore the effects of the rTMS application to other cortical areas, and study how it influences time interval interpretation.

Cognitive outcomes of TMS treatment in bipolar depression: Safety data from a randomized controlled trial.

BACKGROUND: Bipolar depression (BD) is a highly prevalent condition associated with marked cognitive deficits that persist even in the euthymic phase of the illness. Pharmacological treatments for BD might further aggravate cognitive impairment, highlighting the need of developing interventions that present cognitive safety. In this study, we evaluated the cognitive effects of H1-coil (deep) transcranial magnetic stimulation (TMS) in patients with treatment-resistant bipolar depression. METHODS: Fourty-three patients were randomized to receive 20 sessions of active (55 trains, 18 Hz, 120% resting motor threshold intensity) or sham rTMS within a double-blind, sham-controlled trial. A battery of 20 neuropsychological assessments, grouped in 6 domains (attention and processing speed, working memory and executive function, inhibitory control, language, immediate verbal memory, and long-term verbal memory) was performed at baseline and after 4 and 8 weeks of trial onset. Depressive symptoms were assessed with the 17-item Hamilton Rating Scale for Depression. RESULTS: Cognitive improvement was shown for all cognitive domains. It occurred regardless of intervention group and depression improvement. For the language domain, greater improvement was observed in the sham group over time. No correlations between depression (at baseline or during treatment) and cognitive improvement were found. LIMITATIONS: Absence of healthy control group. CONCLUSION: The results of this exploratory study provide evidence on the cognitive safety of H1-coil TMS for BD patients. Putative pro-cognitive effects of rTMS in BD were not observed and thus should be further investigated.

Primed Low Frequency Transcranial Magnetic Stimulation Effects on Smoking Cue-Induced Craving

Abstract Repetitive Transcranial Magnetic Stimulation (rTMS) has shown the potential to reduce craving to smoke and the amount of cigarettes smoked. When low frequency rTMS is preceded by a priming session the cortical inhibitory effects are enhanced provoking a lasting performance. In this study we evaluate the brain regional activations and self-reported mood effect of one session of primed low frequency rTMS over the left dorsolateral prefrontal cortex (DLPFC) in response to smoking- related cues during temporary nicotine abstinence. Ten moderate nicotine dependent subjects participated in a crossover design, comparing a single session of active versus sham stimulation. After treatment, a functional Magnetic Resonance Imaging (fMRI) study was performed in all participants while completing a block-design cue reactivity paradigm. Our measures also included self-reported craving and mood score before and after every rTMS session. The number of daily smoked cigarette in a one week around period was also recorded. The results show that self-reported cravings were lower following the active stimulation; significant activation was found in areas associated with emotion control (anterior cingulate gyrus and subgenual area) and episodic memory (precuneus and posterior cingulate gyrus) as a result of the stimulation. No significant difference was found in the number of cigarettes smoked and mood scores between the sham and active condition during the one week period records. This study confirms the previous evidence that rTMS can reduce cigarette cravings and provides evidence of the neural mechanism of action that take place in order to achieve these neuromodulation effects.

Resumen La Estimulación Magnética Transcranea repetitiva (EMTr) ha demostrado ser capaz de reducir el deseo por fumar y el consume de cigarrillos. Cuando una baja frecuencia de EMTr es precedida por una sesión de primado, los efectos inhibidores de la corteza cerebral aumentan y también su duración. En este estudio se evalúan las activaciones regionales del cerebro y el efecto en el estado de ánimo auto-reportado de una sesión de EMTr de baja frecuencia primada sobre la corteza dorsolateral prefrontal izquierda en respuesta a estímulos visuales relacionados con el tabaco durante una abstinencia temporal a la nicotina. Diez sujetos con dependencia moderada a la nicotina participaron en un experimento de diseño cruzado, comparando una sola sesión de estimulación activa contra una simulada. Después del tratamiento, se llevó a cabo un estudio de Imagen por Resonancia Magnética funcional (IRMf) en todos los participantes mientras llevaban a cabo un paradigma visual de bloques. Las mediciones incluyeron una puntuación auto-reportada del deseo por fumar y estado de ánimo antes y después de cada sesión de EMTr. Los resultados muestran que el deseo por fumar era menor luego de una sesión activa de estimulación; se encontraron activaciones significativas en áreas asociadas con el control emocional (giro del cíngulo anterior) y memoria episódica (precúneo y giro del cíngulo posterior) como resultado de la estimulación. No se encontró diferencia significativa en el número de cigarros fumados entre la sesión activa y simulado durante el periodo evaluado. Tampoco se registraron diferencias en las evaluaciones de estado de ánimo luego del tratamiento. Este estudio confirma la evidencia previa de que la EMTr puede reducir el deseo por fumar y proporciona evidencia del mecanismo de acción neural que se lleva a cabo para lograr estos efectos neuromoduladores.

A systematic review and meta-analysis of the use of repetitive transcranial magnetic stimulation for auditory hallucinations treatment in refractory schizophrenic patients.

BACKGROUND: The use of repetitive transcranial magnetic stimulation (rTMS) remains a promising therapeutic tool in the treatment of schizophrenia. Symptoms such as auditory hallucinations (AH) find contradictory results in many studies. Here we present an up-to-date systematic review and meta-analysis of rTMS in the treatment of AH in schizophrenia. METHODS: We searched Pubmed-MEDLINE from 1999 to 2013 for double-blinded randomized sham-controlled trials that applied slow rTMS on the left temporoparietal cortex and assessed the outcome results using Hallucination Change Scale or Auditory Hallucination Rating Scale or Scale for Auditory Hallucinations (SAH). We identified 10 studies suitable for the meta-analysis. RESULTS: We found a positive sized effect in favor of rTMS [random-effects model Hedges' g = 0.011, I-squared = 58.1%]. There was some variability between study effect sizes, but the sensitivity analysis concluded that none of them had sufficient weight to singularly alter the results of our meta-analysis. DISCUSSION: rTMS appears to be an effective treatment for AH. The left temporoparietal cortex seems to be the area in which rTMS is effective. Although meta-analysis is a powerful analytical tool, more studies must be conducted in order to obtain a more expressive sample size to perform a more accurate analytical approach.

Efficacy of coupling repetitive transcranial magnetic stimulation and physical therapy to reduce upper-limb spasticity in patients with stroke: a randomized controlled trial.

OBJECTIVE: To assess the efficacy of inhibitory repetitive transcranial magnetic stimulation (rTMS) for decreasing upper-limb muscle tone after chronic stroke. DESIGN: A randomized sham-controlled trial with a 4-week follow-up. SETTING: Research hospital. PARTICIPANTS: Patients with stroke (N=20) with poststroke upper limb spasticity. INTERVENTIONS: The experimental group received rTMS to the primary motor cortex of the unaffected side (1500 pulses; 1Hz; 90% of resting motor threshold for the first dorsal interosseous muscle) in 10 sessions, 3d/wk, and physical therapy (PT). The control group received sham stimulation and PT. MAIN OUTCOME MEASURES: Modified Ashworth scale (MAS), upper-extremity Fugl-Meyer assessment, FIM, range of motion, and stroke-specific quality-of-life scale. All outcomes were measured at baseline, after treatment (postintervention), and at a 4-week follow-up. A clinically important difference was defined as a reduction of ≥1 in the MAS score. RESULTS: Friedman test revealed that PT is efficient for significantly reducing the upper limb spasticity of patients only when it is associated with rTMS. In the experimental group, 90% of the patients at postintervention and 55.5% at follow-up showed a decrease of ≥1 in the MAS score, representing clinically important differences. In the control group, 30% of the patients at postintervention and 22.2% at follow-up experienced clinically meaningful changes. There were no differences between the groups at any time for any of the other outcome measures, indicating that both groups demonstrated similar behaviors over time for all variables. CONCLUSIONS: rTMS associated with PT can be beneficial in reducing poststroke spasticity. However, more studies are needed to clarify the clinical changes underlying the reduction in spasticity induced by noninvasive brain stimulations.

Análisis de fuentes del EEG en pacientes tratados con estimulación magnética transcraneal a 5 Hz como tratamiento antidepresivo / Electroencephalographic source analysis in patients receiving 5-Hz transcranial magnetic stimulation as antidepressant treatment

Transcranial Magnetic Stimulation (rTMS) is a technique that allows noninvasive electrical stimulation of the cortex with few side effects. An antidepressant effect has been proposed when rTMS is delivered over prefrontal dorsolateral cortex (DLPFC) ≥5Hz. Quantitative EEG studies have shown increases in alpha and theta power bands as well as frontal interhemispheric asymmetries in most recordings from depressed patients. rTMS over left DLPFC at 5Hz involve a safer and more tolerable procedure, and its neurophysiological correlates has not been explored using EEG source analysis. The aim of this research was to study changes in EEG sources using VARTERA method in a group of patients with major depressive disorder (MDD) treated with 5Hz rTMS over left DLPFC as single or combined treatment with escitalopram. Methods 18 patients with DSM-IV MDD diagnosis without treatment for the current episode were included. Subjects were randomly assigned to one of two groups: A) rTMS+escitalopram 10mg, n=9; B) rTMS+placebo, n=9. Subjects received 15 sessions of rTMS on a daily basis. In order to compare changes in EEG sources two recordings were obtained, prior and after treatment. HDRS, BDI and HARD were used for clinical assessments. Results All patients of group A and eight patients of group B showed response to treatment (considered as a reduction of 50% in HDRS score). An increase in absolute power at 9.37Hz and 10.17Hz in temporal and postcentral gyrus on the left hemisphere was found in group B. Absolute power in those frequencies was decreased in the same regions for group A. In addition, an increased power in beta band frequencies was observed in both hemispheres for group A. Conclusion Increases in alpha band could be the hallmark of the 5Hz rTMS, but it could be reduced by escitalopram. Besides, increases observed in beta band for group A could be related to escitalopram effect.

La estimulación magnética transcraneal repetitiva (EMTr) es una técnica que permite estimular eléctricamente la corteza cerebral de manera no invasiva y con pocos efectos secundarios. Se ha propuesto que la EMTr aplicada sobre la corteza prefrontal dorsolateral (CPFDL) izquierda con frecuencias ≥5Hz tiene efectos antidepresivos. Se ha encontrado que en el electroencefalograma cuantitativo (QEEG por sus siglas en inglés) la mayoría de pacientes deprimidos presentan incrementos en las bandas theta y alfa, así como asimetrías interhemisféricas en la actividad alfa en regiones anteriores. La EMTr sobre la CPFDL izquierda a 5Hz ofrece ventajas considerables en seguridad y tolerabilidad; sin embargo, sus correlatos neurofisiológicos no han sido explorados por el análisis de fuentes del EEG. Objetivo Estudiar los cambios en las fuentes del EEG según el método VARETA en un grupo de pacientes con trastorno depresivo mayor que recibieron EMTr a 5Hz sobre la corteza prefrontal dorsolateral izquierda como tratamiento único o en combinación con escitalopram. Material y métodos Se estudiaron 18 pacientes con diagnóstico de trastorno depresivo mayor de acuerdo con los criterios del DSM-IV sin tratamiento para el episodio en curso. Los sujetos habían sido aleatoriamente asignados a uno de los siguientes grupos de tratamiento: A) EMTr+escitalopram 10mg, n=9; B) EMTr+placebo, n=9. Se aplicó EMTr, a 5Hz en una sesión diaria durante 15 días. Se obtuvieron dos registros electroencefalográficos, uno basal y otro final, con el fin de comparar los cambios en las fuentes de actividad eléctrica cerebral, pretratamiento y post-tratamiento. Se realizaron evaluaciones clinimétricas con las escalas de Hamilton para Depresión y Ansiedad y el Inventario de Depresión de Beck. Resultados Todos los pacientes en el grupo A y ocho pacientes en el grupo B respondieron al tratamiento, con una reducción de 50% o más en la escala HDRS. En el análisis de fuentes se encontró un efecto en el grupo B caracterizado por incremento en la PA de 9.37 a 10.17Hz, en regiones temporales y giro poscentral izquierdos, mismo que se encontró disminuido en el grupo A, Además se encontró un incremento en fracuencias correspondientes a la banda beta en regiones frontales de ambos hemisferios en el grupo A. Conclusiones Podría considerarse que el incremento en la banda alfa es característico de la EMTr a 5Hz, mismo que se ve reducido por efecto del escitalopram. Por otro lado, se observó que el grupo A mostró incrementos en fuentes correspondientes a la banda beta como posible efecto relacionado del fármaco antidepresivo.

Clinical and electrophysiological effect of right and left repetitive transcranial magnetic stimulation in patients with major depressive disorder / Efecto clínico y electrofisiológico de la estimulación magnética transcraneal repetitiva derecha e izquierda en pacientes con transtorno depresivo mayor

Major Depressive Disorder (MDD) is a common psychiatric disorder that represents one of the main public health problems worldwide. It has been projected that for 2020 it will be the second cause of disability-adjusted life years just below ischemic heart disease. Quantitative electroencephalogram provides the opportunity to study cortical oscillatory activity across the different frequency bands. It constitutes an accessible tool to explore the clinical and neurophysiologic correlates underlying psychiatric disorders as well as the effect of diverse therapeutic options and the performance through cognitive tasks. Repetitive transcranial magnetic stimulation is a technique that allows the stimulation of the cerebral cortex noninvasively, relatively painlessly and with fairly few side effects. The vast majority of rTMS studies target left dorsolateral prefrontal cortex (DLPFC) based on imaging studies showing that left prefrontal cortex dysfunction is pathophysiologically linked to depression. However, there is some evidence implicating right PFC in the pathophysiology of depression. Comparison of antidepressant efficacy of diverse stimulation frequencies is relevant since a main concern around rTMS is its potential to induce seizures; hence we consider that frequency of stimulation is an important aspect to be studied. For this study we aimed to elucidate the clinical efficacy of rTMS comparing two groups of depressed patients stimulated over DLPFC, one over the left (at 5 Hz) and other over the right (at 1 Hz). We also meant to know if there were clinical and electroencephalographic differential long-term after-effects between those groups of treatment. We included twenty right-handed patients with a DSM-IVR diagnosis of MDD. They were assigned into two groups of treatment. Group 1 received 5Hz rTMS over the left DLPFC. Group 2 received 1Hz rTMS over the right DLPFC. We obtained two EEG measurements in order to analyze Z score of broad-band spectral parameters and cross-spectral. No statistical differences among groups were found in response to treatment after weekly comparisons of clinimetric scores and significant differences between baseline and final assessment by HDRS, MADRS, BDI and HARS. The major rTMS effect on EEG was observed in the group that received 1 Hz over the right DLPFC and no significant effects were observed for the group that received 5 Hz over the left DLPFC. Our results propose that administration of 15 sessions on either left (5 Hz) or right (1 Hz) rTMS over DLPFC is sufficient to reach response to treatment, assessed by HDRS, MADRS, BDI and HARS in subjects with MDD. Moreover, in both cases rTMS was able to induce an equivalent antidepressant effect. The major effect of rTMS on EEG was observed in the right 1 Hz rTMS group where changes were elicited mainly over frontal, central and temporal regions on alpha and particularly beta frequency bands. In a lesser extent for left 5 Hz rTMS group the main effect was observed on anterior regions for beta and particularly alpha frequency bands. We believe it is pertinent to continue exploring the therapeutic potential of lower stimulation frequencies, for what further research including larger samples is still necessary to confirm these trends.

El trastorno depresivo mayor es una entidad psiquiátrica que representa uno de los principales problemas de salud pública a nivel mundial. Se ha proyectado que para el año 2020 será la segunda causa de discapacidad únicamente por debajo de la cardiopatía isquémica. La utilización del electroencefalograma cuantitativo ofrece la oportunidad de estudiar la actividad oscilatoria cortical a través de las diferentes bandas de frecuencias. Éste constituye una herramienta para explorar las características clínicas y neurofisiológicas que subyacen a los trastornos psiquiátricos, así como un instrumento para evaluar el efecto de diversas opciones terapéuticas y el desempeño de los sujetos durante la realización de tareas cognitivas. La estimulación magnética transcraneal repetitiva (EMTr) es una técnica que permite la estimulación de la corteza cerebral de manera no invasiva, relativamente sin dolor y con pocos efectos secundarios. Con base en los estudios de neuroimagen que vinculan la fisiopatología de la depresión con disfunción en la corteza prefrontal dorsolateral (CPFDL), la mayoría de las investigaciones se han enfocado en estimular dicha corteza en el hemisferio izquierdo. No obstante, existen pruebas que implican a la corteza prefrontal derecha con la fisiopatología de la depresión. La relevancia de comparar la eficacia antidepresiva de diversas frecuencias radica en el hecho de que un tema de interés particular alrededor de la EMTr es su potencial para inducir convulsiones, por ello consideramos que la exploración de las diversas frecuencias de estimulación con efecto terapéutico constituye un aspecto importante de estudio. Para este trabajo nos propusimos determinar la eficacia antidepresiva de la EMTr comparando dos grupos de pacientes que fueron estimulados en la CPFDL derecha a 1 Hz o en la izquierda a 5 Hz. También buscamos dilucidar si existen diferencias clínicas y electroencefalográficas a largo plazo entre grupos de tratamiento. Para este estudio se incluyeron 20 pacientes con diagnóstico de trastorno depresivo mayor de acuerdo con los criterios del DSM-I V. Los sujetos fueron asignados aleatoriamente a uno de dos grupos de tratamiento. Un grupo recibió EMTr sobre la CPFDL izquierda a 5Hz; el otro recibió estimulación a 1 Hz sobre la corteza contralateral. Se obtuvieron dos registros electroencefalográficos, uno basal y otro final, con el fin de comparar las medidas espectrales de banda ancha y estrecha, pretratamiento y postratamiento. Se realizaron evaluaciones clinimétricas con las escalas de Hamilton para Depresión y Ansiedad, la escala de Depresión de Montgomery-Asberg y el Inventario de Beck. No encontramos diferencias significativas al comparar la respuesta a la EMTr entre ambos grupos. Los pacientes de ambos grupos presentaron respuesta a tratamiento (disminución de ≥50% de la sintomatología depresiva) medida por clinimetría. El efecto más importante de la EMTr sobre el EEG se observó en el grupo de estimulación derecha a 1 Hz donde encontramos disminución postratamiento en los valores Z de banda estrecha alfa y beta, principalmente en regiones fronto-centro-temporales. Aunque en menor proporción, en el grupo de estimulación izquierda a 5 Hz encontramos incrementos significativos post EMTr, predominantemente en las bandas beta y alfa sobre todo en regiones anteriores. No se encontraron resultados significativos en el análisis de banda ancha. Nuestros resultados sugieren que la administración de 15 sesiones de EMTr ya sea sobre la CPFDL derecha (1 Hz) o izquierda (5 Hz) es capaz de lograr respuesta antidepresiva. Nuestros hallazgos electrofisiológicos sugieren que uno de los efectos a largo plazo de la EMTr es la reorganización de los circuitos neuronales implicados en la depresión.

Low frequency (0.5Hz) rTMS over the right (non-dominant) motor cortex does not affect ipsilateral hand performance in healthy humans / A inibição do córtex motor não-dominante por meio da estimulação magnética transcraniana a 0, 5Hz não interfere no desempenho manual ipsilateral de sujeitos hígidos

Reduction of excitability of the dominant primary motor cortex (M1) improves ipsilateral hand function in healthy subjects. In analogy, inhibition of non-dominant M1 should also improve ipsilateral performance. In order to investigate this hypothesis, we have used slow repetitive transcranial magnetic stimulation (rTMS) and the Purdue Pegboard test. Twenty-eight volunteers underwent 10 minutes of either 0.5Hz rTMS over right M1 or sham rTMS (coil perpendicular to scalp). The motor task was performed before, immediately after, and 20 minutes after rTMS. In both groups, motor performance improved significantly throughout the sessions. rTMS inhibition of the non-dominant M1 had no significant influence over ipsilateral or contralateral manual dexterity, even though the results were limited by unequal performance between groups at baseline. This is in contrast to an improvement in left hand function previously described following slow rTMS over left M1, and suggests a less prominent physiological transcallosal inhibition from right to left M1.

A redução da excitabilidade do córtex motor primário (M1) dominante melhora o desempenho manual ipsilateral: a inibição do M1 não-dominante poderia, analogamente, aprimorar a função manual direita. Para investigar esta hipótese, utilizou-se a estimulação magnética transcraniana repetitiva (EMTr) de baixa frequência e o teste Purdue Pegboard. Submetemos 28 voluntários a 10 minutos de EMTr sobre o M1 direito (0,5 Hz) ou a EMTr placebo (bobina perpendicular ao escalpo). O teste foi executado antes, imediatamente após e 20 minutos após a EMTr. Nos dois grupos, o desempenho manual mostrou significativa melhora entre as sessões. A inibição do M1 não-dominante não influenciou significativamente a destreza motora ipsi ou contralateral, apesar da conclusão limitada pelo desempenho discrepante dos grupos na primeira sessão. Este resultado contrasta com a melhora da função manual esquerda descrita após a EMTr sobre o M1 esquerdo e sugere uma inibição transcalosa fisiológica menos intensa do M1 direito para o esquerdo.