TMS application in both health and disease

Transcranial magnetic stimulation (TMS) can be useful for therapeutic purposes for a variety of clinical conditions. Numerous studies have indicated the potential of this non-invasive brain stimulation technique to recover brain function and to study physiological mechanisms. Following this line, the articles contemplated in this Research Topic show that this field of knowledge is rapidly expanding and considerable advances have been made in the last few years. There are clinical protocols already approved for Depression (and anxiety comorbid with major depressive disorder), Obsessive compulsive Disorder (OCD), migraine headache with aura, and smoking cessation treatment but many studies are concentrating their efforts on extending its application to other diseases, e.g., as a treatment adjuvant. In this Research Topic we have the example of using TMS for pain, post-stroke depression, or smoking cessation, but other diseases/injuries of the central nervous system need attention (e.g., tinnitus or the surprising epilepsy). Further, the potential of TMS in health is being explored, in particular regarding memory enhancement or the mapping of motor control regions, which might also have implications for several diseases.publishe

O Impacto das Novas Terapêuticas no Mieloma Múltiplo

Introdução: O mieloma múltiplo é a segunda neoplasia hematológica mais comum nos países desenvolvidos e a sua incidência é maior na faixa etária entre os 65 e os 75 anos. Caracteriza-se pela proliferação monoclonal de plasmócitos, dando origem a lesões de órgão-alvo, conhecidas por CRAB: hipercalcemia, lesão renal, anemia e lesões osteolíticas. O paradigma em relação ao tratamento aplicado nesta neoplasia tem mudado de forma drástica ao longo dos últimos anos e espera-se que nos próximos anos ainda evolua mais. Objetivo: Perceber de que forma os tratamentos evoluíram ao longo dos anos e o impacto que tiveram no prognóstico dos doentes, principalmente ao nível da sobrevida global e da sobrevivência livre de progressão, é o objetivo primordial deste trabalho. Método: Como metodologia para a realização desta monografia foi utilizado o motor de busca PubMed, e foram, igualmente, retirados alguns artigos do Blood Cancer Journal. Foram impostos limites temporais na pesquisa, à exceção dos artigos referenciados no capítulo “Abordagem Histórica, os quais não obedeceram a nenhum limite temporal. A prioridade foram sempre os artigos mais recentes e apenas em língua inglesa. Desenvolvimento: O mieloma múltiplo é resultado da evolução de uma gamapatia monoclonal de significado indeterminado devido à influência de alterações genéticas e epigenéticas adquiridas ao longo do tempo. É uma neoplasia de difícil diagnóstico, porque pode ser confundida clinicamente com muitas outras entidades, daí que o prognóstico do doente também dependa muito da fase em que é diagnosticada. Historicamente, o mieloma múltiplo foi uma doença que durante muitas décadas foi de difícil controlo, porque através dos tratamentos utilizados não se obtinham taxas de resposta satisfatórias. Só a partir da década de 90 do século passado, com a aplicação do transplante autólogo de progenitores hematopoiéticos e anos mais tarde com o surgimento dos imunomoduladores, dos inibidores do proteossoma e dos anticorpos monoclonais, é que foi possível melhorar muito o prognóstico dos doentes, tanto a nível da sobrevida global média que aumentou de 3 para 8 a 10 anos, nas últimas duas décadas, como a nível da qualidade de vida, devido às remissões mais duradouras que os doentes experienciam. Conclusão: O mieloma múltiplo é atualmente considerado uma doença crónica devido ao impacto altamente positivo que as novas terapêuticas têm apresentado ao nível da sobrevida global e da sobrevida livre de progressão. No entanto, sabe-se que as recaídas são inevitáveis e que a doença desenvolve resistências contra o tratamento. Por isso há ainda muito para investigar, principalmente na área da imunoterapia, que pode constituir a chave para a cura e/ou prevenção do mieloma múltiplo.Introduction: Multiple myeloma is the second most common haematological malignancy in developed countries, and its incidence is higher in the age range between 65 and 75 years old. It is characterized by the monoclonal proliferation of plasma cells, leading to end organ damage known as CRAB: hypercalcaemia, renal impairment, anaemia, and osteolytic bone lesions. The paradigm regarding treatment for this neoplasm has changed dramatically in recent years, and it is expected to continue evolving in the upcoming years. Objective: The main objective of this work is to understand how treatments have evolved over the years and the impact they have had on patient prognosis, especially in terms of overall survival and progression-free survival. Method: The PubMed search engine was used as the methodology for this monograph, and some articles were also retrieved from the Blood Cancer Journal. Time limits were imposed on the search, except for the articles referenced in the "Abordagem Histórica" chapter, which did not follow any time limit. Priority was always given to the most recent articles and those only in English. Discussion: Multiple myeloma results from the evolution of a monoclonal gammopathy of undetermined significance due to the influence of genetic and epigenetic changes acquired over time. It is a neoplasm that is difficult to diagnose because it can be clinically similar to other diseases. Therefore, the patient's prognosis also depends on the stage at which it is diagnosed. Historically, multiple myeloma was a disease that was difficult to control because the treatments used did not produce deep response rates. Only from the 1990s, with the application of autologous hematopoietic stem cell transplantation, and later with the emergence of immunomodulatory agents, proteasome inhibitors, and monoclonal antibodies, it has been possible to significantly improve the prognosis of patients, both in terms of median overall survival, which has increased from 3 to 8-10 years in the last two decades, and in terms of quality of life due to more durable remissions experienced by patients. Conclusion: Multiple myeloma is currently considered a chronic disease due to the highly positive impact of new therapies on overall survival and progression-free survival. However, it is known that relapses are inevitable, and that the disease develops drug resistance. Therefore, there is still much to investigate, especially in the area of immunotherapy, which may hold the key to the cure and/or prevention of multiple myeloma

Do psychogenic erectile dysfunction and premature ejaculation share a neural circuit?: evidence from a fMRI systematic review and meta-analysis

Background: Several functional magnetic resonance imaging (fMRI) studies investigated the brain correlates of psychogenic erectile dysfunction (PED) and premature ejaculation (PE), representing the most common sexual dysfunctions in men. These studies allowed a wide set of brain regions in PED and PE patients when compared to healthy men. In the present meta-analysis, we aim at assessing the presence of homogeneity in the cerebral underpinnings of PED and PE. Methods: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and after the electronic search, duplicate removal and the application of pre-exclusion criteria, nine PED and ten PE studies were considered eligible with a Cohen’s k of 0.84 and 0.75, respectively. The effect sizes of the sociodemographic and psychological/urological dimensions were calculated. We extracted brain clusters from the retrieved studies, comparing patients and controls, and we calculated brain maps with Seed-Based D Mapping software. Results: We found a homogenous involvement of the frontal gyrus and insula in both dysfunctions, suggesting a common network. Conclusions: The anterior insula plays a key role in the processing of emotional features of stimuli, while the posterior insula in interoceptive information is relevant for sexual response. The prefrontal and inferior frontal cortices are important for sexual inhibition/disinhibition

Continuous theta burst stimulation increases contralateral mu and beta rhythms with arm elevation:implications for neurorehabilitation

The study of the physiological effects underlying brain response to transcranial magnetic stimulation is important to understand its impact on neurorehabilitation. We aim to analyze the impact of a transcranial magnetic stimulation protocol, the continuous theta burst (cTBS), on human neurophysiology, particularly on contralateral motor rhythms. cTBS was applied in 20 subjects over the primary motor cortex. We recorded brain electrical activity pre- and post-cTBS with electroencephalography both at rest and while performing motor tasks, to evaluate changes in brain oscillatory patterns such as mu and beta rhythms. Moreover, we measured motor-evoked potentials before and after cTBS to assess its impact on brain's excitability. On the hemisphere contralateral to the protocol, we did observe a significant increase in mu (p = 0.027) and beta (p = 0.006) rhythms from pre- to post-cTBS, at the beginning of arm elevation. The topology of action planning and motor execution suggests that cTBS produced an inhibitory effect that propagated to the contralateral hemisphere, thereby precluding the expected/desired excitation for therapy purposes. This novel approach provides support for the notion that this protocol induces inhibitory changes in contralateral motor rhythms, by decreasing desynchronization, contradicting the ipsilateral inhibition vs. contralateral disinhibition hypothesis. Our results have implications for personalized cTBS usage as a rehabilitation intervention, suggesting that an unexpected propagation of inhibition can occur

Ressonância Magnética Cerebral Funcional: qual o Impacto e que Limites?

A ressonância magnética functional(RMf) é uma técnica ainda relativamente recente, tendo surgido no início dos anos 90 do século passado, quando Ogawa(Ogawa et al., 1992) e Bandettini (Bandettini et al., 1992) demonstraram que o sinal hemodinâmico BOLD, com origem no contraste de sinal T2*, se alterava de forma correspondente ao padrão de estimulação sensorial. Esta técnica permaneceu controversa desde o início, pois embora traduzisse padrões de neuroativação, só em 2001 Logothetis e colegas (Logothetis et al., 2001) demonstraram de forma direta que a modulação do sinal BOLD (dependente do nível de oxigenação sanguínea, do Inglês Blood-oxygen-level-dependent) refletia de facto a atividade neuronal

The role of anterior and posterior insula in male genital response and in visual attention: an exploratory multimodal fMRI study

Several studies highlighted the role of insula on several functions and in sexual behavior. This exploratory study examines the relationships among genital responses, brain responses, and eye movements, to disentangle the role played by the anterior and posterior insula during different stages of male sexual response and during visual attention to sexual stimuli. In 19 healthy men, fMRI, eye movement, and penile tumescence data were collected during a visual sexual stimulation task. After a whole-brain analysis comparing neutral and sexual clips and confirming a role for the bilateral insulae, we selected two bilateral seed regions in anterior and posterior insula for functional connectivity analysis. Single-ROI-GLMs were run for the FC target regions. Single-ROI-GLMs were performed based on areas to which participants fixate: "Faces", "Genitals," and "Background" with the contrast "Genitals > Faces". Single-ROI-GLMs with baseline, onset, and sustained PT response for the sexual clips were performed. We found stronger effects for the posterior than the anterior insula. In the target regions of the posterior insula, we found three different pathways: the first involved in visual attention, onset of erection, and sustained erection; the second involved only in the onset of erection, and the third limited to sustained erection

In vitro degradation and in vivo biocompatibility of chitosan-poly(butylene succinate) fiber mesh scaffolds

In tissue engineering, the evaluation of the host response to the biomaterial implantation must be assessed to determine the extent of the inflammatory reaction. We studied the degradation of poly(butylene succinate) and chitosan in vitro using lipase and lysozyme enzymes, respectively. The subcutaneous implantation of the scaffolds was performed to assess tissue response. The type of inflammatory cells present in the surrounding tissue, as well as within the scaffold, was determined histologically and by immunohistochemistry. In the presence of lipase or lysozyme, the water uptake of the scaffolds increased. Based on the weight loss data and scanning electron microscopy analysis, the lysozyme combined with lipase had a notable effect on the in vitro degradation of the scaffolds. The in vivo implantation showed a normal inflammatory response, with presence of neutrophils, in a first stage, and macrophages, lymphocytes, and giant cells in a later stage. Vascularization in the surrounding tissue and within the implant increased with time. Moreover, the collagen deposition increased with time inside the implant. In vivo, the scaffolds maintained the structural integrity. The degradation in vitro was faster and greater compared to that observed in vivo within the same time periods.Ana R Costa-Pinto was supported by the scholarship SFRH/24735/2005 from the Portuguese “Fundação para a Ciência e a Tecnologia” (FCT). This work was partially supported by the European Network of Excellence EXPERTISSUES (NMP3-CT-2004-500283) and FCT funded project Maxbone (PTDC/ SAU-ENB/115179/2009)