Motor cortical inhibitory deficits in patients with obsessive-compulsive disorder–A systematic review and meta-analysis of transcranial magnetic stimulation literature

Funding Information: DR was supported by H2020-SC1-DTH-2019-875358-FAITH. AM and GC are supported by Fundação para a Ciência e Tecnologia (FCT) through Ph.D. Scholarships (respectively, SFRH/BD/144508/2019 and SFRH/BD/130210/2017). GC and AO-M are supported by grant FCT-PTDC/MED-NEU/31331/2017, funded by FCT/MCTES. AO-M was funded by a Starting Grant from the European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement no. 950357). JB-C and AO-M were supported by grant FCT-PTDC/MEC-PSQ/30302/2017-IC&DT-LISBOA-01-0145-FEDER, funded by national funds from FCT/MCTES and co-funded by FEDER, under the Partnership Agreement Lisboa 2020–Programa Operacional Regional de Lisboa. JO was supported by BBRF-27595-2018 NARSAD. None of the agencies had a role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, in the preparation, review, or approval of the manuscript, nor in the decision to submit the manuscript for publication. Publisher Copyright: Copyright © 2022 Rodrigues da Silva, Maia, Cotovio, Oliveira, Oliveira-Maia and Barahona-Corrêa.Introduction: Obsessive-compulsive disorder (OCD) is a highly prevalent chronic disorder, often refractory to treatment. While remaining elusive, a full understanding of the pathophysiology of OCD is crucial to optimize treatment. Transcranial magnetic stimulation (TMS) is a non-invasive technique that, paired with other neurophysiological techniques, such as electromyography, allows for in vivo assessment of human corticospinal neurophysiology. It has been used in clinical populations, including comparisons of patients with OCD and control volunteers. Results are often contradictory, and it is unclear if such measures change after treatment. Here we summarize research comparing corticospinal excitability between patients with OCD and control volunteers, and explore the effects of treatment with repetitive TMS (rTMS) on these excitability measures. Methods: We conducted a systematic review and meta-analysis of case-control studies comparing various motor cortical excitability measures in patients with OCD and control volunteers. Whenever possible, we meta-analyzed motor cortical excitability changes after rTMS treatment. Results: From 1,282 articles, 17 reporting motor cortex excitability measures were included in quantitative analyses. Meta-analysis regarding cortical silent period shows inhibitory deficits in patients with OCD, when compared to control volunteers. We found no statistically significant differences in the remaining meta-analyses, and no evidence, in patients with OCD, of pre- to post-rTMS changes in resting motor threshold, the only excitability measure for which longitudinal data were reported. Discussion: Our work suggests an inhibitory deficit of motor cortex excitability in patients with OCD when compared to control volunteers. Cortical silent period is believed to reflect activity of GABAB receptors, which is in line with neuroimaging research, showing GABAergic deficits in patients with OCD. Regardless of its effect on OCD symptoms, rTMS apparently does not modify Resting Motor Threshold, possibly because this measure reflects glutamatergic synaptic transmission, while rTMS is believed to mainly influence GABAergic function. Our meta-analyses are limited by the small number of studies included, and their methodological heterogeneity. Nonetheless, cortical silent period is a reliable and easily implementable measurement to assess neurophysiology in humans, in vivo. The present review illustrates the importance of pursuing the study of OCD pathophysiology using cortical silent period and other easily accessible, non-invasive measures of cortical excitability. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020201764], identifier [CRD42020201764].publishersversionpublishe

Repetitive Transcranial Magnetic Stimulation for Treatment of Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder manifesting as lifelong deficits in social communication and interaction, as well as restricted repetitive behaviors, interests and activities. While there are no specific pharmacological or other physical treatments for autism, in recent years repetitive Transcranial Magnetic Stimulation (rTMS), a technique for non-invasive neuromodulation, has attracted interest due to potential therapeutic value. Here we report the results of a systematic literature review and meta-analysis on the use of rTMS to treat ASD.Methods: We performed a systematic literature search on PubMed, Web of Science, Science Direct, Bielefeld Academic Search, and Educational Resources Information Clearinghouse. Search terms reflected diagnoses and treatment modalities of interest. Studies reporting use of rTMS to treat core ASD or cognitive symptoms in ASD were eligible. Two researchers performed article selection and data extraction independently, according to PRISMA guidelines. Changes in ASD clinical scores or in cognitive performance were the main outcomes. Random effects meta-analysis models were performed.Results: We found 23 eligible reports, comprising 4 case-reports, 7 non-controlled clinical trials, and 12 controlled clinical trials, comparing the effects of real TMS with waiting-list controls (n = 6) or sham-treatment (n = 6). Meta-analyses showed a significant, but moderate, effect on repetitive and stereotyped behaviors, social behavior, and number of errors in executive function tasks, but not other outcomes. Most studies had a moderate to high risk of bias, mostly due to lack of subject- and evaluator-blinding to treatment allocation. Only 5 studies reported stability of these gains for periods of up 6 months, with descriptions that improvements were sustained over time.Conclusions: Existing evidence supports that TMS could be useful to treat some dimensions of ASD. However, such evidence must be regarded with care, as most studies did not adequately control for placebo effects. Moreover, little is known regarding the most effective stimulation parameters, targets, and schedules. There is an urgent need for further randomized, double-blind, sham-controlled trials, with adequate follow-up periods, to test the efficacy of transcranial magnetic stimulation to treat these disorders. Available evidence must be regarded as preliminary and insufficient, at present, to support offering TMS to treat ASD

Hepatocyte growth factor signalizes peritoneal membrane failure in peritoneal dialysis

BACKGROUND: Hepatocyte growth factor (HGF) counteracts peritoneal fibrosis in animal models and in-vitro studies, but no study explored effluent HGF in peritoneal dialysis (PD) patients with ultrafiltration failure (UFF). Our aim was to assess the relationship between effluent HGF with UF profile, free water transport (FWT) and small-solute transport. METHODS: We performed 4-hour, 3.86% PET with additional UF measurement at 60 minutes in 68 PD patients. MTACcreatinine, FWT, small-pore ultrafiltration, and effluent HGF were quantified. RESULTS: Effluent HGF negatively correlated with UF (r=-0.80, p=0.009) and FWT (r=-0.69, p=0.04). Patients with UFF had higher dialysate HGF (103 pg/mL vs 77 pg/mL, p=0.018) and, although not statistically significant, those with FWT compromise had also higher dialysate HGF compared with subgroup of UFF without FWT compromise (104 pg/mL vs 88 pg/mL, p=0.08). FWT≤45% without clinical UFF was documented in some patients who also had increased effluent HGF. CONCLUSIONS: Dialysate HGF concentration is significantly higher among patients with UFF, specially, if FWT is impaired, being a sign of peritoneal membrane deterioration.This study was partially performed with the help of investigations grants from Sociedade Portuguesa de Nefrologia. This work was also supported by UMIB/ICBAS – University of Porto (UP). Multidisciplinary Unit for Biomedical Research (UMIB) is funded by grants from Foundation for Science and Technology (Fcomp-01-0124-FEDER-015896

A Systematic Review and Meta-Analysis

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder manifesting as lifelong deficits in social communication and interaction, as well as restricted repetitive behaviors, interests and activities. While there are no specific pharmacological or other physical treatments for autism, in recent years repetitive Transcranial Magnetic Stimulation (rTMS), a technique for non-invasive neuromodulation, has attracted interest due to potential therapeutic value. Here we report the results of a systematic literature review and meta-analysis on the use of rTMS to treat ASD. Methods: We performed a systematic literature search on PubMed, Web of Science, Science Direct, Bielefeld Academic Search, and Educational Resources Information Clearinghouse. Search terms reflected diagnoses and treatment modalities of interest. Studies reporting use of rTMS to treat core ASD or cognitive symptoms in ASD were eligible. Two researchers performed article selection and data extraction independently, according to PRISMA guidelines. Changes in ASD clinical scores or in cognitive performance were the main outcomes. Random effects meta-analysis models were performed. Results: We found 23 eligible reports, comprising 4 case-reports, 7 non-controlled clinical trials, and 12 controlled clinical trials, comparing the effects of real TMS with waiting-list controls (n = 6) or sham-treatment (n = 6). Meta-analyses showed a significant, but moderate, effect on repetitive and stereotyped behaviors, social behavior, and number of errors in executive function tasks, but not other outcomes. Most studies had a moderate to high risk of bias, mostly due to lack of subject- and evaluator-blinding to treatment allocation. Only 5 studies reported stability of these gains for periods of up 6 months, with descriptions that improvements were sustained over time. Conclusions: Existing evidence supports that TMS could be useful to treat some dimensions of ASD. However, such evidence must be regarded with care, as most studies did not adequately control for placebo effects. Moreover, little is known regarding the most effective stimulation parameters, targets, and schedules. There is an urgent need for further randomized, double-blind, sham-controlled trials, with adequate follow-up periods, to test the efficacy of transcranial magnetic stimulation to treat these disorders. Available evidence must be regarded as preliminary and insufficient, at present, to support offering TMS to treat ASD.publishersversionpublishe

How the interplay between neuroscience and phenomenology changed our understanding of obsessive-compulsive disorder

The understanding of obsessive-compulsive disorder (OCD) has evolved with the knowledge of behavior, the brain, and their relationship. Modern views of OCD as a neuropsychiatric disorder originated from early lesion studies, with more recent models incorporating detailed neuropsychological findings, such as perseveration in set-shifting tasks, and findings of altered brain structure and function, namely of orbitofrontal corticostriatal circuits and their limbic connections. Interestingly, as neurobiological models of OCD evolved from cortical and cognitive to sub-cortical and behavioral, the focus of OCD phenomenology also moved from thought control and contents to new concepts rooted in animal models of action control. Most recently, the proposed analogy between habitual action control and compulsive behavior has led to the hypothesis that individuals suffering from OCD may be predisposed to rely excessively on habitual rather than on goal-directed behavioral strategies. Alternatively, compulsions have been proposed to result either from hyper-valuation of certain actions and/or their outcomes, or from excessive uncertainty in the monitoring of action performance, both leading to perseveration in prepotent actions such as washing or checking. In short, the last decades have witnessed a formidable renovation in the pathophysiology, phenomenology, and even semantics, of OCD. Nevertheless, such progress is challenged by several caveats, not least psychopathological oversimplification and overgeneralization of animal to human extrapolations. Here we present an historical overview of the understanding of OCD, highlighting converging studies and trends in neuroscience, psychiatry and neuropsychology, and how they influenced current perspectives on the nosology and phenomenology of this disorder.publishersversionpublishe

What is it that every “educated person” should know? Universal and local knowledge in two versions of an encyclopedia of children and youth

En este trabajo analizaremos comparativamente las ediciones en español y portugués de la enciclopedia El Tesoro de la Juventud. Así como en varios países del mundo, las traducciones de la enciclopedia The Book of Knowledge tuvieron enorme suceso editorial en Brasil y Argentina. Esta fue la primera enciclopedia dirigida al público infanto–juvenil y se volvió un libro de referencia en bibliotecas y escuelas de los dos países. Gran parte de los asuntos tratados fue traducida sin alteraciones en los diferentes idiomas, lo que contribuyó para universalizar conocimientos y abordajes producidos en otros locales. Sin embargo, es importante observar que en los mismos textos pueden encontrarse diferentes encuadres,dando para cada caso coloraciones disímiles en el tratamiento de determinados temas. Es interesante marcar igualmente que, siendo la versión en español común a diversos países latinoamericanos, sus editores tuvieron que tejer difíciles tramas de unificación. En estas líneas recortamos la mirada a las primeras ediciones de cada versión, y la comparación de los libros equivalentes de Cosas que debemos saber, Hombres y mujeres célebres, el Libro de la América Latina. Intentaremos dar cuenta de explicar las semejanzas y diferencias encontradas que traigan significaciones para los lectores de una y otra traducción. La gran repercusión de esta obra educativa a nivel mundial hace de ella un excelente objeto de estudio del proceso de circulación internacional de modelos y saberes, y de sus apropiaciones locales.In this work we will comparatively analyze the Spanish and Portuguese editions of El Tesoro de la Juventud. As well as in various countries in the world the translations of The Book of Knowledge had a huge editorial success in Brazil and Argentina. This was the first encyclopedia addressed to children and youth public and has become a reference book in libraries and schools of both countries. Big part of the matters discussed was translated without changes in both different languages, which contributed to universalize knowledge and approaches produced in other locations. It’s important to note, notwithstanding, that in the same texts it’s possible to find different outlines, providing each case with different nuances in the treatment of certain matters. It’s our interest to highlight that, being the Spanish version common to many Latin American countries, their editorials had to come up with difficult unification plots. On these Pagès we point out the first editions of each version, and the comparison of the equivalent books, Cosas que debemos saber, Hombres y mujeres célebres, and el Libro de la América Latina. We intend to explain the similarities and differences found that demonstrate significations to the readers of one and the other translations. The repercussion of this educational work to a worldwide level makes it an excellent international circulation of patterns and knowledge research object as well as its local appropriations.Facultad de Humanidades y Ciencias de la Educació

What is it that every “educated person” should know? Universal and local knowledge in two versions of an encyclopedia of children and youth

En este trabajo analizaremos comparativamente las ediciones en español y portugués de la enciclopedia El Tesoro de la Juventud. Así como en varios países del mundo, las traducciones de la enciclopedia The Book of Knowledge tuvieron enorme suceso editorial en Brasil y Argentina. Esta fue la primera enciclopedia dirigida al público infanto–juvenil y se volvió un libro de referencia en bibliotecas y escuelas de los dos países. Gran parte de los asuntos tratados fue traducida sin alteraciones en los diferentes idiomas, lo que contribuyó para universalizar conocimientos y abordajes producidos en otros locales. Sin embargo, es importante observar que en los mismos textos pueden encontrarse diferentes encuadres,dando para cada caso coloraciones disímiles en el tratamiento de determinados temas. Es interesante marcar igualmente que, siendo la versión en español común a diversos países latinoamericanos, sus editores tuvieron que tejer difíciles tramas de unificación. En estas líneas recortamos la mirada a las primeras ediciones de cada versión, y la comparación de los libros equivalentes de Cosas que debemos saber, Hombres y mujeres célebres, el Libro de la América Latina. Intentaremos dar cuenta de explicar las semejanzas y diferencias encontradas que traigan significaciones para los lectores de una y otra traducción. La gran repercusión de esta obra educativa a nivel mundial hace de ella un excelente objeto de estudio del proceso de circulación internacional de modelos y saberes, y de sus apropiaciones locales.In this work we will comparatively analyze the Spanish and Portuguese editions of El Tesoro de la Juventud. As well as in various countries in the world the translations of The Book of Knowledge had a huge editorial success in Brazil and Argentina. This was the first encyclopedia addressed to children and youth public and has become a reference book in libraries and schools of both countries. Big part of the matters discussed was translated without changes in both different languages, which contributed to universalize knowledge and approaches produced in other locations. It’s important to note, notwithstanding, that in the same texts it’s possible to find different outlines, providing each case with different nuances in the treatment of certain matters. It’s our interest to highlight that, being the Spanish version common to many Latin American countries, their editorials had to come up with difficult unification plots. On these Pagès we point out the first editions of each version, and the comparison of the equivalent books, Cosas que debemos saber, Hombres y mujeres célebres, and el Libro de la América Latina. We intend to explain the similarities and differences found that demonstrate significations to the readers of one and the other translations. The repercussion of this educational work to a worldwide level makes it an excellent international circulation of patterns and knowledge research object as well as its local appropriations.Facultad de Humanidades y Ciencias de la Educació

Role of Adiponectin in Coronary Heart Disease Risk:A Mendelian Randomization Study

RATIONALE: Hypoadiponectinemia correlates with several coronary heart disease (CHD) risk factors. However, it is unknown whether adiponectin is causally implicated in CHD pathogenesis. OBJECTIVE: We aimed to investigate the causal effect of adiponectin on CHD risk. METHODS AND RESULTS: We undertook a Mendelian randomization study using data from genome-wide association studies consortia. We used the ADIPOGen consortium to identify genetic variants that could be used as instrumental variables for the effect of adiponectin. Data on the association of these genetic variants with CHD risk were obtained from CARDIoGRAM (22 233 CHD cases and 64 762 controls of European ancestry) and from CARDIoGRAMplusC4D Metabochip (63 746 cases and 130 681 controls; ≈ 91% of European ancestry) consortia. Data on the association of genetic variants with adiponectin levels and with CHD were combined to estimate the influence of blood adiponectin on CHD risk. In the conservative approach (restricted to using variants within the adiponectin gene as instrumental variables), each 1 U increase in log blood adiponectin concentration was associated with an odds ratio for CHD of 0.83 (95% confidence interval, 0.68–1.01) in CARDIoGRAM and 0.97 (95% confidence interval, 0.84–1.12) in CARDIoGRAMplusC4D Metabochip. Findings from the liberal approach (including variants in any locus across the genome) indicated a protective effect of adiponectin that was attenuated to the null after adjustment for known CHD predictors. CONCLUSIONS: Overall, our findings do not support a causal role of adiponectin levels in CHD pathogenesis