La neuroplasticidad y el reaprendizaje / Neuroplasticity and relearning

El presente articulo tiene por objetivo analizar la neuro plasticidad del cerebro y el reaprendizaje a partir del caso de Chery Schiltz presentado por Doidge (2018) en su libro: El cerebro se cambia asimismo. El método utilizado es el analítico sintético y la técnica de sustentación documental. El trabajo estudia ciertas ideas de la Neuro plasticidad que superar la concepción de la inmutabilidad del cerebro vinculadas a la idea de que el cerebro está conformado por módulos especializados; asimismo, se reflexiona sobre la imposibilidad de visualizar la neuro plasticidad solamente desde el ámbito fisiológico mecanicista, sin contemplar el proceso volutivo del individuo, lo que nos abre a la posibilidad de la inherente relación entre la Neuro plasticidad y el reaprendizaje.

Técnicas de Neuroimagenología en la Cuantificación de la Neuroplasticidad en Pacientes con Enfermedad Vascular Cerebral / Neuroimaging Techniques for Neuroplasticity Quantification in Stroke Patients

RESUMEN Las técnicas de neuroimagenología otorgan información relevante del estado funcional y anatómico del cerebro humano. Esta información es particularmente importante cuando existe una lesión cerebral causada por alguna patología, tal como la enfermedad vascular cerebral (EVC). En pacientes afectados por esta enfermedad, se ha determinado que la neuroplasticidad es el mecanismo principal de recuperación de la función motora perdida. Debido a la alta prevalencia de la EVC a nivel mundial y especialmente en países en vías de desarrollo, es necesario continuar investigando los mecanismos de recuperación involucrados en esta patología. La resonancia magnética funcional (RMF) y la imagenología por tensor de difusión (ITD) son dos de las técnicas de neuroimagenología más utilizadas con este fin. La RMF permite analizar la actividad neuronal generada al ejecutar tareas de movimiento, mientras que la ITD proporciona información estructural de la anatomía cerebral. En esta revisión narrativa, se presentan diversos estudios que han utilizado estas técnicas de neuroimagenología en la cuantificación de los cambios de neuroplasticidad en pacientes con EVC tras participar en algún programa de neurorrehabilitación. Comprender mejor estos cambios de neuroplasticidad permitiría diseñar esquemas de rehabilitación que proporcionen un mayor beneficio a los pacientes con EVC.

ABSTRACT Neuroimaging techniques provide relevant information of the functional and anatomical status of the human brain. This information is of particular importance when a pathology, like stroke, produces a brain injury. In stroke patients, it has been determined that neuroplasticity is the primary recovery mechanism of the lost motor function. Due to worldwide high prevalence, especially in developing countries, it is necessary to continue the research of the recovery mechanisms involved in this pathology. To this end, functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) are two of the most used neuroimaging techniques. In stroke patients, fMRI allows the analysis of the neural activity produced by the execution of motor tasks, whereas DTI provides structural information of the brain anatomy. In this narrative review, multiple studies that employ these neuroimaging techniques for quantification of neuroplasticity changes in stroke patients after undergoing a neurorehabilitation program are presented. Better understanding of these neuroplasticity changes would allow researchers to design and provide more beneficial rehabilitation schemes to stroke patients.

Neurorrehabilitación funcional de miembro superior tras ictus en lobulo parietal derecho. Revisión / Functional neurorehabilitation of the upper limb after stroke in the right parietal lobe. Review

Objetivos: profundizar en las diferentes técnicas de rehabilitación funcional de los miembros superiores afectados por una lesión neurológica en el lóbulo parietal tras un ictus, empleando métodos y/o abordajes que estén apoyados por diferentes marcos teóricos de referencia, dentro de la Neurorrehabilitación y la Terapia ocupacional. Métodos: en total han sido seleccionados 30 documentos para llevar a cabo la revisión bibliográfica, en inglés y español, utilizando buscadores como PubMed, Dialnet, Scielo, páginas web. Resultados: se muestran diferentes intervenciones terapéuticas que abordan de forma integral al paciente (función cognitiva, sensitiva y motora). Se diferencian terapias convencionales y modernas, existiendo dentro de estas últimas otras clasificaciones dependiendo de si utilizan dispositivos externos para lograr la reorganización cortical o métodos internos inherentes al paciente. Conclusiones: el inicio del tratamiento tras un daño parietal en hemisferio derecho debe ser lo más temprano posible y la mejor evidencia recae sobre el reaprendizaje orientado a tareas, que aumenta si a ésta se suman otras terapias, para abordar de forma integral las distintas áreas afectadas del paciente.(AU)

Objective: To delve into the different functional rehabilitation techniques of the upper limbs affected by a neurological lesion in the parietal lobe after a stroke, using methods and/or approaches that are supported by different theoretical frameworks of reference, within Neurorehabilitation and Therapy. occupational. Methods: A total of 30 documents have been selected to carry out the bibliographic review, in English and Spanish, using search engines such as PubMed, Dialnet, Scielo, web pages. Results: Different therapeutic interventions are shown that comprehensively address the patient (cognitive, sensory and motor function). Conventional and modern therapies are differentiated, existing within the latter other classifications depending on whether they use external devices to achieve cortical reorganization or internal methods inherent to the patient. Conclusions: The start of treatment after parietal damage in the right hemisphere should be as early as possible and the best evidence relies on task-oriented relearning, which increases if other therapies are added to it, to comprehensively address the different affected areas. of the patient.(AU)

La plasticidad sináptica mediada por endocannabinoides y trastornos por consumo de drogas / Endocannabinoid-mediated synaptic plasticity and substance use disorders

Las drogas impactan en los circuitos de recompensa cerebrales y originan dependencia y adicción, lo que se define actualmente como trastornos por consumo de drogas. Los mecanismos de plasticidad sináptica en dichos circuitos son cruciales en el desarrollo de la conducta adictiva, y los endocannabinoides, entre los que destacan la anandamida y el 2-araquidonil-glicerol, participan en la normal neuroplasticidad. Se sabe que los trastornos por consumo de drogas se asocian, entre otros fenómenos, a disrupción de la plasticidad sináptica mediada por endocannabinoides. Estas moléculas median neuroplasticidad de corta duración y perdurable. Respecto a la de corta duración, destacan fenómenos de carácter «inhibidor», como la supresión de la inhibición inducida por despolarización y la supresión de la excitación inducida por despolarización; y otros «desinhibidores», como la desinhibición de la actividad neuronal, sobre todo en el núcleo estriado, y la supresión de la liberación GABA en el hipocampo. Por otra parte, las drogas pueden alterar la normal potenciación perdurable y la depresión perdurable mediadas por endocannabinoides. Los endocannabinoides también influyen en el desarrollo de hipofrontalismo y sensibilización causados por las drogas. En fin, el abuso de drogas origina una disrupción en la plasticidad sináptica de circuitos cerebrales involucrados en la adicción y en ello juega un destacado papel la alteración de la normal actividad endocannabinoide. Ello facilita los cambios anómalos cerebrales y el desarrollo de conductas adictivas que caracterizan a los trastornos por consumo de drogas. (AU)

Drugs impact brain reward circuits, causing dependence and addiction, in a condition currently described as substance use disorders. Mechanisms of synaptic plasticity in these circuits are crucial in the development of addictive behaviour, and endocannabinoids, particularly anandamide and 2-arachidonyl-glycerol, participate in normal neuroplasticity. Substance use disorders are known to be associated with disruption of endocannabinoid-mediated synaptic plasticity, among other phenomena. Endocannabinoids mediate neuroplasticity in the short and the long term. In the short term, we may stress «inhibitory» phenomena, such as depolarisation-induced suppression of inhibition and depolarisation-induced suppression of excitation, and such «disinhibitory» phenomena as long-lasting disinhibition of neuronal activity, particularly in the striatum, and suppression of hippocampal GABA release. Drugs of abuse can also disrupt normal endocannabinoid-mediated long-term potentiation and long-term depression. Endocannabinoids are also involved in the development of drug-induced hypofrontality and sensitisation. In summary, substance abuse causes a disruption in the synaptic plasticity of the brain circuits involved in addiction, with the alteration of normal endocannabinoid activity playing a prominent role. This facilitates abnormal changes in the brain and the development of the addictive behaviours that characterise substance use disorders. (AU)

Current evidence on the potential therapeutic applications of transcranial magnetic stimulation in multiple sclerosis: a systematic review of the literature.

INTRODUCTION: A growing number of studies have evaluated the effects of transcranial magnetic stimulation (TMS) for the symptomatic treatment of multiple sclerosis (MS). METHODS: We performed a PubMed search for articles, recent books, and recommendations from the most relevant clinical practice guidelines and scientific societies regarding the use of TMS as symptomatic treatment in MS. CONCLUSIONS: Excitatory electromagnetic pulses applied to the affected cerebral hemisphere allow us to optimise functional brain activity, including the transmission of nerve impulses through the demyelinated corticospinal pathway. Various studies into TMS have safely shown statistically significant improvements in spasticity, fatigue, lower urinary tract dysfunction, manual dexterity, gait, and cognitive deficits related to working memory in patients with MS; however, the exact level of evidence has not been defined as the results have not been replicated in a sufficient number of controlled studies. Further well-designed, randomised, controlled clinical trials involving a greater number of patients are warranted to attain a higher level of evidence in order to recommend the appropriate use of TMS in MS patients across the board. TMS acts as an adjuvant with other symptomatic and immunomodulatory treatments. Additional studies should specifically investigate the effect of conventional repetitive TMS on fatigue in these patients, something that has yet to see the light of day.

Frontiers in the research of autism pathogenesis / Fronteras en la investigación de la patogenia del autismo

Abstract This review focuses on four interrelated teams and research lines that form the basis for new research on the pathogenesis of autism spectrum disorder (ASD) at the Marcus Autism Center, in Atlanta (US). These themes probe typical social behavior and brain development from birth, and disruptions thereof in babies later diagnosed with ASD. These four themes are: to leverage lifetime maximal neuroplasticity; to test the hypothesis that developmental disruption of early-emerging mechanisms of socialization drives pathogenesis and results in autistic social disability; the focus on the infant-caregiver dyad, and the iterative context associated with mutually reinforcing and adapted social and communitive inter-action, or emerging cycles of social contingency, from the first days and weeks of life; and the study of time-varying neurodevelopmental transitions in social behavior from experience-expectant (reflexive, endogenous) and subcortically-guided to experience-dependent (caregiver- and reward-driven) and cortically-guided, a transition that our work suggests is uniquely disrupted in babies later diagnosed with ASD. This science is opening a world of opportunities to optimize children's outcomes despite the genetic liabilities that they are born with. It provides the scientific grounding for new community-viable solutions for increasing access to early interventions using treatments that scaffold and strengthen infant-caregiver interactions, which is the platform for early brain development.

Resumen Esta revisión se centra en cuatro equipos y líneas de investigación interrelacionados que forman la b ase de nuevas investigaciones sobre la patogenia del Trastorno del Espectro Autista (TEA) en el Marcus Autism Center, en Atlanta (EE.UU.). Estos temas investigan el comportamiento social típico y el desarrollo del cerebro desde el nacimiento, y las altera ciones del mismo en los bebés a los que luego se les diagnostica TEA. Estos cuatro temas son: aprovechar la neuroplasticidad máxima en la vida; probar la hipótesis de que la interrupción del desarrollo de los mecanismos de socialización emergentes impulsa la patogénesis y da como resultado una discapacidad social autista; el enfoque en la díada bebé-cuidador, y el contexto iterativo asoc iado con la mutua interacción de refuerzo social y comunitario, o ciclos emergentes de contingencia social, desde los primeros días y semanas de vida; y el estudio de las transiciones del comportamiento social variable en el tiempo del neurodesarrollo desde la experiencia-expectante (reflexiva, endógena) y guiada subcorticalmente, a la experiencia-dependiente (cuidador e impulsado por la recompensa) y guiada corticalmente, una transición que nuestro trabajo sugiere que se interrumpe única mente en bebés diagnosticados posteriormente con TEA.

Endocannabinoid-mediated synaptic plasticity and substance use disorders.

Drugs impact brain reward circuits, causing dependence and addiction, in a condition currently described as substance use disorders. Mechanisms of synaptic plasticity in these circuits are crucial in the development of addictive behaviour, and endocannabinoids, particularly anandamide and 2-arachidonyl-glycerol, participate in normal neuroplasticity. Substance use disorders are known to be associated with disruption of endocannabinoid-mediated synaptic plasticity, among other phenomena. Endocannabinoids mediate neuroplasticity in the short and the long term. In the short term, we may stress "inhibitory" phenomena, such as depolarisation-induced suppression of inhibition and depolarisation-induced suppression of excitation, and such "disinhibitory" phenomena as long-lasting disinhibition of neuronal activity, particularly in the striatum, and suppression of hippocampal GABA release. Drugs of abuse can also disrupt normal endocannabinoid-mediated long-term potentiation and long-term depression. Endocannabinoids are also involved in the development of drug-induced hypofrontality and sensitisation. In summary, substance abuse causes a disruption in the synaptic plasticity of the brain circuits involved in addiction, with the alteration of normal endocannabinoid activity playing a prominent role. This facilitates abnormal changes in the brain and the development of the addictive behaviours that characterise substance use disorders.

Development of an integrative learning program for community dwelling old people with dementia / Desarrollo de un programa de aprendizaje integrador para personas de edad avanzada con demencia que viven en la comunidad / Desenvolvimento de um programa de aprendizagem integrativa para idosos com demência residentes na comunidade

Objective: to develop an integrative learning program for people with dementia. Method: a methodological study was conducted using Delphi technique to develop the learning program, followed by a feasibility test. An expert panel was invited to develop the integrative learning program based on the neuroplasticity and learning framework. A feasibility test was conducted to evaluate the implementation of the program in two centers after the training of personnel who run the program. Verbatim transcripts of case conferences were coded, analyzed, and collapsed into themes and sub-themes by consensus. Results: there was no indication for content modification during the period of program implementation. Qualitatively, the participating older adults showed improvement in communications, emotions, connectedness with self and others, and well-being. Conclusion: the integrative learning program was uneventfully implemented with promising results. The program is ready for full-scale research on its efficacy in multiple centers to obtain more robust evidence.

Objetivo: desarrollar un programa de aprendizaje integrador para personas con demencia. Método: se realizó un estudio metodológico empleando la técnica Delphi para desarrollar el programa de aprendizaje, seguida de una prueba de viabilidad. Se invitó a un panel de expertos a que desarrollara el programa de aprendizaje integrador sobre la base del marco de la neuroplasticidad y el aprendizaje. Se realizó una prueba de viabilidad para evaluar la implementación del programa en dos centros después de haber capacitado al personal que dirige el programa. Las transcripciones literales de los debates de casos se codificaron, analizaron y resumieron en temas y subtemas por medio de consenso. Resultados: no hubo ninguna indicación para modificar el contenido durante el período de implementación del programa. En forma cualitativa, los adultos mayores que participaron del programa evidenciaron mejoras en la comunicación, las emociones, la capacidad de conexión con ellos mismos y con los demás y el bienestar. Conclusión: el programa de aprendizaje integrador se implementó sin inconvenientes con resultados prometedores. El programa es apto para ser sometido a una investigación a gran escala con respecto a su eficacia en varios centros para obtener evidencia más sólida.

Objetivo: desenvolver um programa de aprendizagem integrativa para pessoas com demência. Método: foi realizado um estudo metodológico com a técnica Delphi para desenvolver o programa de aprendizagem, seguido de um teste de viabilidade. Um grupo de especialistas foi convidado para desenvolver o programa de aprendizagem integrativa com base no framework da neuroplasticidade e da aprendizagem. Um teste de viabilidade foi realizado para avaliar a implementação do programa em dois centros após treinamento do pessoal que dirige o programa. Transcrições literais de conferências de casos foram codificadas, analisadas e agrupadas em temas e subtemas por consenso. Resultados: não houve indicação de modificação de conteúdo durante o período de implementação do programa. Qualitativamente, os idosos participantes apresentaram melhora nas comunicações, emoções, conexão consigo e com os outros e bem-estar. Conclusão: o programa de aprendizagem integrativa foi implementado sem intercorrências com resultados promissores. O programa está adequado para ser submetido a pesquisas em grande escala relacionadas com sua eficácia em vários centros a fim de obter evidências mais robustas.

Brain-Computer Interfaces for upper limb motor rehabilitation of stroke patients / Interfaces Cerebro-Computadora para la Rehabilitación Motora de Miembro Superior de Pacientes con Enfermedad Vascular Cerebral

Abstract Brain-Computer Interfaces (BCI) decode users' intentions from the central nervous system and could be applied for upper limb motor rehabilitation of patients that have suffered stroke, one of the main causes of disability worldwide. Despite that research groups have reported the efficacy of these systems, a consensus has not yet been reached regarding their true potential. For this reason, a review of up-to-date assessments of BCI for upper limb stroke rehabilitation is presented from the perspective of analyzing common and different design variables presented across studies. Clinical and pilot studies with a control group were included in the review. Most BCI interventions assessments were performed with robotic assistive devices as feedback, followed by neuromuscular electrical stimulation (NMES) and visual feedbacks. Compared to other experimental interventions, the effects of a BCI intervention have been reported in a low number of patients. In addition, high variability between studies' designs such as stroke etiology and interventions' duration, do not allow to assess the potential of BCI for stroke rehabilitation. However, a trend towards significant rehabilitation outcomes with BCI systems can be highlighted, encouraging research groups to better coordinate in order to make valuable contributions to the field.

Resumen Las interfaces cerebro-computadora (BCI) decodifican del sistema nervioso central las intenciones de los usuarios, y pueden ser aplicadas para la rehabilitación motora del miembro superior de pacientes con enfermedad vascular cerebral (EVC), una de las principales causas de discapacidad a nivel mundial. A pesar de que diversos grupos han reportado la eficacia de estos sistemas, no se ha logrado un consenso sobre su verdadero potencial. Por esta razón, una revisión de la evaluación reciente de las BCI para rehabilitación del miembro superior en la EVC es presentado desde la perspectiva de analizar diferencias y similitudes entre las variables reportadas en los estudios. En la esta revisión se incluyeron estudios clínicos y pilotos con un grupo control. La mayor parte de los estudios utilizaron sistemas robóticos como retroalimentación, seguido por estimulación eléctrica neuromuscular y retroalimentación visual. En comparación con otras terapias experimentales, los efectos de intervenciones con BCI se han reportado en pocos pacientes. Además, la alta variabilidad en el diseño de los estudios, como la etiología de la EVC y la duración de las intervenciones, no permiten comparar los efectos de las terapias BCI. Sin embargo, se puede resaltar una tendencia hacia recuperaciones motoras significativas con BCI, motivando a grupos de investigación a coordinarse de mejor forma para continuar realizando contribuciones al campo.

Medición de reserva cognitiva: estudio en una muestra de adultos chilenos / Cognitive reserve assessment: a study in a sample of chilean adults

Mayor reserva se asocia con resistencia al deterioro en sujetos con enfermedades neurodegenerativas. En personas sanas explica las diferencias interindividuales en el rendimiento de tareas. Medir los factores de reserva cognitiva permite contar con un índice numérico de la ganancia cognitiva acumulada por un sujeto. Este índice puede ser correlacionado con otras funciones cuantificables. El presente trabajo tiene como objetivo presentar los índices de reserva obtenidos por una población chilena en la aplicación del Cognitive Reserve Index Questionnaire (CRIq). Para ello 90 adultos (18-85 años) sin evidencias de trastorno cognitivo, de la región de Valparaíso-Chile, fueron entrevistados sobre actividades de estudio, laborales y de tiempo libre ejecutadas desde los 18 años.Los resultados muestran que los índices de reserva de los sujetos varían en función del tiempo de ejecución de actividades promotoras de reserva y no por su edad. Se encontraron diferencias estadísticamente significativas entre los grupos etarios. Estos resultados permiten concluir que la ejecución de actividades de estudio, laborales, sociales, entre otras aumenta los índices de reserva cognitiva, que es una variable diferenciadora entre individuos. La medición de dichos índices puede ser útil en un amplio campo de disciplinas (medicina, neurología, neuropsicología, educación, psicología, fonoaudiología, neurociencias y en las ciencias cognitivas en general).

A higher cognitive reserve is linked to higher resistance to deterioration among subjects suffering from neurodegenerative disorders. In healthy persons the cognitive reserve explains inter-individual differences in task performance. Measuring the cognitive reserve factors involves obtaining a numerical index of the cumulative cognitive gain accumulated by a subject. This index can be correlated with other measurable functions.This study was conceived to determine the reserve indexes accumulated by a Chilean sample, by means of the administration of the Cognitive Reserve Index Questionnaire (CRIq).In order to do so, 90 adults (18-85 years old) without evidence of cognitive disorder, living in Valparaíso region, Chile, were interviewed about their education, their work environment and their and leisure activities carried out since they were 18 years old.Results showed that reserve indexes of the subjects vary as a function of the time of execution of reserve-promoting activities, not age. Statistically significant differences were found among age-groups. These findings allow us to conclude that studying, working and engaging in social activities, among other things, increase the cognitive reserve indexes, which are a differentiating variable among individuals.The measurement of these indexes can be useful in a wide array of disciplines: medicine, neurology, neuropsychology, education, psychology, phonoaudiology, neurosciences and cognitive sciences in general.

Effect of periapical inflammation on calcium binding proteins and ERK in the trigeminal nucleus / Efecto de la inflamación periapical sobre las proteínas fijadoras de calcio y ERK en el núcleo trigeminal

Peripheral inflammation induces plastic changes in neurons and glia which are regulated by free calcium and calcium binding proteins (CaBP). One of the mechanisms associated with the regulation of intracellular calcium is linked to ERK (Extracellular Signal-Regulated Kinase) and its phosphorylated condition (pERK). ERK phosphorylation is important for intracellular signal transduction and participates in regulating neuroplasticity and inflammatory responses. The aim of this study is to analyse the expression of two CaBPs and pERK in astrocytes and neurons in rat trigeminal subnucleus caudalis (Vc) after experimental periapical inflammation on the left mandibular first molar. At seven days post-treatment, the periapical inflammatory stimulus induces an increase in pERK expression both in S100b positive astrocytes and Calbindin D28k positive neurons, in the ipsilateral Vc with respect to the contralateral side and control group. pERK was observed coexpressing with S100b in astrocytes and in fusiform Calbindin D28k neurons in lamina I. These results could indicate that neural plasticity and pain sensitization could be maintained by ERK activation in projection neurons at 7 days after the periapical inflammation.

La inflamación periférica induce cambios plásticos en las neuronas y en la glía, los cuales están regulados por el calcio libre y las proteínas fijadoras calcio (CaBP). Uno de los mecanismos asociados con la regulación del calcio intrace-lular está vinculado con la fosforilación de la pro teína quinasa ERK. Asimismo, ERK fosforilado es importante para la trans-ducción de señales intracelulares y participa en la regulación de la neuroplasticidad y las respuestas inflamatorias. El objetivo de este estudio es analizar la expresión de dos CaBPs y pERK en astrocitos y neuronas del subnúcleo caudal del trigémino (Vc) después de una inflamación periapical experimental en el primer molar inferior izquierdo en ratas. A los siete días posteriores al tratamiento, el estímulo inflamatorio periapical induce un aumento en la expresión de pERK, en el número de astrocitos positivos para la proteína marcadora astroglial S100b y en neuronas positivas para Calbindina D28k, en el Vc ipsilateral respecto del lado contralateral y el grupo de control. Además, se observó coexpresión de pERK tanto en astrocitos S100b positivos, como en neuronas fusiformes Calbindin D28k positivas, de la lámina I. Estas observaciones podrían indicar que la neuroplasticidad y la sensibilización al dolor podrían mantenerse mediante la activación de ERK en las neuronas de proyección a los 7 días de la inflamación periapical.

Mecanismos neurofisiológicos de la rehabilitación vestibular / Neurophysiological mechanisms of vestibular rehabilitation

RESUMEN La rehabilitación vestibular es un concepto terapéutico utilizado en pacientes que presentan síntomas como vértigos y/o mareos, asociados a una afectación vestibular, además de otras manifestaciones clínicas. Este artículo busca entregar un análisis amplio de los elementos que interactúan para definir una patología, como a su vez intervenir en su compensación. Serán presentados elementos neuroanatómicos, fisiológicos y conceptuales de la rehabilitación para este tipo de pacientes con un enfoque clínico basados en la evidencia.

ABSTRACT Vestibular rehabilitation is a therapeutic concept used in patients suffering from dizziness and/or dizziness, in addition to other clinical manifestations. This article gives a broad analysis of the elements that interact to define a pathology, as well as to intervene in their compensation. Neuro anatomical, physiological and conceptual elements of rehabilitation for this type of patients will be presented with a clinical approach based on evidence.

Endocannabinoid-mediated synaptic plasticity and substance use disorders. / La plasticidad sináptica mediada por endocannabinoides y «trastornos por consumo de drogas¼.

Drugs impact brain reward circuits, causing dependence and addiction, in a condition currently described as substance use disorders. Mechanisms of synaptic plasticity in these circuits are crucial in the development of addictive behaviour, and endocannabinoids, particularly anandamide and 2-arachidonyl-glycerol, participate in normal neuroplasticity. Substance use disorders are known to be associated with disruption of endocannabinoid-mediated synaptic plasticity, among other phenomena. Endocannabinoids mediate neuroplasticity in the short and the long term. In the short term, we may stress «inhibitory¼ phenomena, such as depolarisation-induced suppression of inhibition and depolarisation-induced suppression of excitation, and such «disinhibitory¼ phenomena as long-lasting disinhibition of neuronal activity, particularly in the striatum, and suppression of hippocampal GABA release. Drugs of abuse can also disrupt normal endocannabinoid-mediated long-term potentiation and long-term depression. Endocannabinoids are also involved in the development of drug-induced hypofrontality and sensitisation. In summary, substance abuse causes a disruption in the synaptic plasticity of the brain circuits involved in addiction, with the alteration of normal endocannabinoid activity playing a prominent role. This facilitates abnormal changes in the brain and the development of the addictive behaviours that characterise substance use disorders.

Current evidence on the potential therapeutic applications of transcranial magnetic stimulation in multiple sclerosis: A systematic review of the literature. / Evidencias actuales sobre las potenciales aplicaciones terapéuticas de la estimulación magnética transcraneal en la esclerosis múltiple: revisión sistemática de la literatura.

INTRODUCTION: A growing number of studies have evaluated the effects of transcranial magnetic stimulation (TMS) for the symptomatic treatment of multiple sclerosis (MS). METHODS: We performed a PubMed search for articles, recent books, and recommendations from the most relevant clinical practice guidelines and scientific societies regarding the use of TMS as symptomatic treatment in MS. CONCLUSIONS: Excitatory electromagnetic pulses applied to the affected cerebral hemisphere allow us to optimise functional brain activity, including the transmission of nerve impulses through the demyelinated corticospinal pathway. Various studies into TMS have shown statistically significant improvements in spasticity, fatigue, lower urinary tract dysfunction, manual dexterity, gait, and cognitive deficits related to working memory in patients with MS; however, the exact level of evidence has not been defined as the results have not been replicated in a sufficient number of controlled studies. Further well-designed, randomised, controlled clinical trials involving a greater number of patients are warranted to attain a higher level of evidence in order to recommend the appropriate use of TMS in MS patients across the board. TMS acts as an adjuvant with other symptomatic and immunomodulatory treatments. Additional studies should specifically investigate the effect of conventional repetitive TMS on fatigue in these patients, something that has yet to see the light of day.

Current evidence on transcranial magnetic stimulation and its potential usefulness in post-stroke neurorehabilitation: Opening new doors to the treatment of cerebrovascular disease. / Evidencias actuales sobre la estimulación magnética transcraneal y su utilidad potencial en la neurorrehabilitación postictus: Ampliando horizontes en el tratamiento de la enfermedad cerebrovascular.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) is a therapeutic reality in post-stroke rehabilitation. It has a neuroprotective effect on the modulation of neuroplasticity, improving the brain's capacity to retrain neural circuits and promoting restoration and acquisition of new compensatory skills. DEVELOPMENT: We conducted a literature search on PubMed and also gathered the latest books, clinical practice guidelines, and recommendations published by the most prominent scientific societies concerning the therapeutic use of rTMS in the rehabilitation of stroke patients. The criteria of the International Federation of Clinical Neurophysiology (2014) were followed regarding the inclusion of all evidence and recommendations. CONCLUSIONS: Identifying stroke patients who are eligible for rTMS is essential to accelerate their recovery. rTMS has proven to be safe and effective for treating stroke complications. Functional brain activity can be optimised by applying excitatory or inhibitory electromagnetic pulses to the hemisphere ipsilateral or contralateral to the lesion, respectively, as well as at the level of the transcallosal pathway to regulate interhemispheric communication. Different studies of rTMS in these patients have resulted in improvements in motor disorders, aphasia, dysarthria, oropharyngeal dysphagia, depression, and perceptual-cognitive deficits. However, further well-designed randomized controlled clinical trials with larger sample size are needed to recommend with a higher level of evidence, proper implementation of rTMS use in stroke subjects on a widespread basis.

Neuroplasticidad y ácidos grasos omega 3 en adultos mayores / Neuroplasticity and omega-3 fatty acids in older adults

El aumento en la expectativa de vida ha llevado a que las enfermedades neurodegenerativas relacionadas con la vejez sean más investigadas. Las diversas intervenciones no farmacológicas en el campo de las demencias tienen su punto de partida en el concepto de neuroplasticidad o capacidad plástica del cerebro. Se conoce como neuroplasticidad a la capacidad cerebral para minimizar los efectos de las lesiones a través de cambios estructurales y funcionales, lo que permite al cerebro reaccionar o ajustarse a cambios ambientales internos y externos bajo condiciones fisiológicas y patológicas, a través modificaciones morfológicas extensas, como las que se observan en la regeneración de axones, formación de nuevas sinapsis, promoción de la neurogénesis, hasta sutiles cambios moleculares que alteran la respuesta celular a los neurotransmisores. Se ha propuesto como una de las estrategias en el tratamiento de la Enfermedad de Alzheimer, el deterioro cognitivo leve y las intervenciones post ACV la suplementación con ácidos grasos poliinsaturados (AGPI). Los AGPI omega 3 (AGPI ω-3) poseen múltiples mecanismos de acción en el cerebro y en el sistema vascular que podrían generar cierta protección contra el declive cognitivo y la demencia. Los estudios encontrados que fueron realizados en humanos corresponden a pacientes con deterioro cognitivo leve y enfermedad de Alzheimer (EA) leve a moderada y en un solo trabajo se evaluó la suplementación con omega 3 en pacientes post ACV. Aunque la evidencia clínica es algo contradictoria, probablemente en gran parte debido a cuestiones metodológicas, diversos estudios han demostrado que los AGPI ω-3 pueden mejorar la función cognitiva en los individuos adultos sanos y atenuar el deterioro cognitivo en el envejecimiento y EA leve. En los pacientes con EA moderada no se observaron cambios significativos. Hasta hoy no existen resultados concluyentes para incluir a los AGPI omega 3 como parte de un protocolo de tratamiento en enfermedades neurodegenerativas. Se necesitan más estudios aleatorizados controlados para definir el tiempo, dosis y momento adecuado para la prescripción de estos ácidos grasos.

The increase in life expectancy has led to the fact that the neurodegenerative diseases related to old age are being more and more researched. The various non-pharmacological interventions in the field of dementias have their starting point in the concept of neuroplasticity or plastic capacity of the brain. Neuroplasticity is known as the brain capacity to minimize the effects of injuries through structural and functional changes, allowing the brain to react or adjust to internal and external environmental changes under physiological and pathological conditions, through extensive morphological modifications, as the ones observed in the regeneration of axons, formation of new synapses, promotion of neurogenesis, to subtle molecular changes that alter the cellular response to neurotransmitters. It has been proposed as one of the strategies in the treatment of Alzheimer's Disease (AD), mild cognitive impairment (MCI) and poststroke interventions with polyunsaturated fatty acid (PUFA) supplementation. The omega-3 PUFAs (ω-3PUFA) have multiple mechanisms of action in the brain and vascular system that could provide some protection against cognitive decline and dementia. The studies found that were performed in humans correspond to patients with mild cognitive impairment and mild to moderate AD and in only one study, supplementation with omega-3 in poststroke patients was evaluated. Although clinical evidence is somehow contradictory, probably largely due to methodological issues, several studies have shown that ω-3 PUFAs may improve cognitive function in healthy adult individuals and attenuate cognitive impairment in aging and mild AD. No significant changes were observed in patients with moderate AD. Until today, there are no conclusive results to include omega-3 PUFAs as part of a treatment protocol in neurodegenerative diseases. Further randomized controlled studies are needed to define the time, dose and appropriate timing for the prescription of these fatty acids.

Prevalencia, causas y tratamiento de la depresión Mayor / Prevalence, Causes, and Treatment of Major Depression

Resumen La depresión mayor representa un problema de salud pública debido a su alta prevalencia. La etiología de la depresión es compleja ya que en ella intervienen factores psicosociales, genéticos, y biológicos. Entre los factores psicosociales, se ha observado que los primeros episodios depresivos aparecen después de algún evento estresante, y el estrés que acompaña al primer episodio produce cambios a largo plazo en la fisiología cerebral que pueden producir variaciones a nivel estructural y en el funcionamiento de diferentes áreas cerebrales. Entre los factores genéticos que intervienen en el trastorno depresivo, se ha reportado que alrededor de 200 genes están relacionados con el trastorno depresivo mayor. Dentro de los factores biológicos, existen evidencias de alteraciones a nivel de neurotransmisores, citosinas y hormonas, cuyas acciones inducen modificaciones estructurales y funcionales en el sistema nervioso central, en el sistema inmunológico y en el sistema endocrino, que incrementan el riesgo de padecer la depresión mayor. A pesar de años de estudio, las bases biológicas del trastorno depresivo mayor y el mecanismo preciso de la eficacia antidepresiva siguen siendo poco claras. El objetivo de la presente revisión es resumir las principales conclusiones de la literatura clínica y experimental en relación con la etiología del trastorno depresivo mayor.

Abstract Major depression represents a public health problem due to its high prevalence. The etiology of major depression is complex because involves psychosocial, genetic, and biological factors. Among psychosocial factors, different studies report that the first depressive episode appear after some stressful event and produces long-term changes in brain physiology. These long-lasting changes produce variations at the structural level and in the functioning of different brain areas. Among the genetic factors involved in depressive illness, it has been reported that about 200 genes are related to major depressive disorder. Within the biological factors, there is an evidence of alterations in the level of neurotransmitters, cytosine's and hormones, whose actions induces structural and functional modifications in the central nervous system, the immune system and the endocrine system, which increases the risk of suffering major depression. Despite years of study, the biological basis of major depression and precise mechanisms of antidepressant efficacy remain unclear. The objective of the present review is to summarize the main conclusions of the clinical and experimental literature regarding to the etiology of major depressive disorder.

[Patterns of brain ageing]. / Patrones de envejecimiento cerebral.

Neuroplasticity lends the brain a strong ability to adapt to changes in the environment that occur during ageing. Animal models have shown alterations in neurotransmission and imbalances in the expression of neural growth factor. Changes at the morphometric level are not constant. Volume loss is related to alterations in neuroplasticity and involvement of the cerebral neuropil. Although there are no conclusive data, physical exercise improves the molecular, biological, functional and behavioural-cognitive changes associated with brain ageing. The aged human brain has been described as showing weight and volume loss and increased ventricular size. However, neuroimaging shows significant variation and many healthy elderly individuals show no significant macroscopic changes. In most brain regions, the number of neurons remains stable throughout life. Neuroplasticity does not disappear with ageing, and changes in dendritic arborization and the density of spines and synapses are more closely related to brain activity than to age. At the molecular level, although the presence of altered Tau and ß-amyloid proteins is used as a biomarker of neurodegenerative disease, postmortem studies show that these abnormal proteins are common in the brains of elderly people without dementia. Finally, due to the relationship between neurodegenerative diseases and metabolic alterations, this article analyses the influence of insulin-like growth factor and ageing, both in animal models and in humans, and the possible neuroprotective effect of insulin.

Reserva cognitiva en la esclerosis múltiple. Su rol en la evaluación e intervención neuropsicológica / Cognitive reserve in the multiple sclerosis. It´s roll in the evaluation and neuropsychological intervention

Fundamento: Existe una gran variabilidad del funcionamiento cognitivo en el curso de la esclerosis múltiple, incluso entre pacientes que tienen similares patrones de disfunción cerebral. Objetivo: Sintetizar los resultados científicos más representativos sobre las particularidades de la reserva cognitiva en esta patología. Desarrollo: Se sintetiza sobre los referentes teóricos y científicos relacionados con el modelo de reserva cognitiva y cerebral en la esclerosis múltiple, bases neurobiológicas de la reserva y el valor de las actividades cognitivas de ocio como proxies de la reserva cognitiva. Además, se analizan los resultados relacionados con la importancia de la intervención temprana en la prevención del deterioro cognitivo en estos pacientes. Conclusiones: La teoría de la reserva cognitiva puede resultar de gran utilidad para la práctica de la evaluación e intervención neuropsicológica en los pacientes con esclerosis múltiple; en este sentido, la reserva cognitiva puede actuar como un factor modulador (riesgo o protector) del declive cognitivo y marcador de eficiencia cerebral en este tipo de pacientes.

Background: A great variability of the cognitive functioning exists in the course of the multiple sclerosis, even among patients that have similar patterns of cerebral dysfunction. Objective: To synthesize the most representative scientific results about the particularities of the cognitive reservation in this pathology. Development: It is synthesized on the theoretical and scientific referents related with the pattern of cognitive and cerebral reservation in the multiple sclerosis, base neurobiological of the reservation and the value of the leisure cognitive activities like proxies of the cognitive reservation. Also, the results related with the importance of the early intervention are analyzed in the prevention of the cognitive deterioration in these patients. Conclusions: The theory of the cognitive reservation can be of great utility for the practice of the neuropsychological evaluation and intervention in the patients with multiple sclerosis; in this sense, the cognitive reservation can act as a modulator factor (risk or protective) of the cognitive decline and marker of cerebral efficiency in this type of patient.

[Non-pharmacological treatment of cognitive impairment]. / Tratamiento no farmacológico del deterioro cognitivo.

This article reviews the effect of non-pharmacological therapies in persons with cognitive impairment, especially treatments aimed at brain stimulation and functional maintenance, since both pharmacological and non-pharmacological therapies affecting the cognitive and psychoaffective domains are reviewed in another article in this supplement. The article also discusses the close and reciprocal relationship between cognitive impairment, diet and nutritional status and describes the main nutritional risk factors and protective factors in cognitive decline.